MSRC Latest MS Research News

CogniFit coaches MS patients to improve memory & cognition

Fri, 19 Mar 2010 04:58:00 EST

CogniFit�, Inc., a leading maker of Brain Fitness Software, announced a new, independent study that shows CogniFit Personal Coach brain training software improves the cognitive function and skills of Multiple Sclerosis (MS) patients. Many people with MS suffer some cognitive impairment as a result of disease. Patients who trained with the program showed significant improvement in 10 fundamental cognitive skills. Results of this study are published in the current issue of NeuroRehabilitation. During this study, one group of MS patients used CogniFit Personal Coach software for 20-30 minutes, three times a week for 12 weeks, and a control group did not participate in any training. For those individuals who used CogniFit Personal Coach, memory skills showed the greatest improvement. The training group exhibited a general memory increase of 21%, a visual working memory increase of 20% and a verbal-auditory working memory increase of 20% over and beyond that of the control group. Post-hoc, finer-grained analyses of the data showed that linguistic short-term and working memory had improved by 14% and 16% respectively in the cognitive training group over and beyond improvements in the control group. The post-hoc analyses also revealed that participants in the cognitive training group were exhibiting significant improvements, over those in the control group, in naming speed (9%), speed of object recall (10%), focused attention (8%), visuo-motor attention (10%) and visual spatial working memory (8%). The study also examined the unprompted and voluntary adherence rate of MS patients to cognitive training and results show that despite fatigue, a common characteristic side-effect of MS, the majority of the patients (71%) adhered to the training program. Patients who did not adhere were younger than patients who adhered, and in those patients severity of the disease was lower. MS is a chronic inflammatory disease that causes lesions in the nervous system. As part of the nervous system, the brain often sustains some of this damage, leading to cognitive impairment. Although attention/concentration and processing speed, as well as executive functions such as verbal fluency, concept formation, abstract reasoning, planning and monitoring are commonly affected by MS, memory is one of the areas that is most compromised. Researchers believe that CogniFit Personal Coach's ability to target the areas that need training most led to the dramatic improvements seen particularly across the different types of memory. "While patients in the cognitive training group were significantly improving vital cognitive functions using an enjoyable cognitive intervention at home, in the control group cognitive growth was often non-existent," said Dr. Evelyn Shatil, article author and Head of Cognitive Science at CogniFit. "We also observed high real-life adherence rates for patients with neurological disorders who trained - unprompted and voluntarily - in the privacy of their homes. Together, the findings offer great hope for comprehensive home-based personalized medicine which combines cognitive training interventions with medication therapy." CogniFit Personal Coach provides scientifically validated cognitive training that is tailored to meet the specific needs of individuals. Following a baseline assessment, users engage in exercises designed to train their brain which continually adjust to the level of the user. As a result, people using CogniFit software are challenged enough to improve their abilities, but not frustrated by the software's difficulty level. As users' skills improve, the training also evolves. Previous studies using the CogniFit Personal Coach software have shown its ability to improve cognitive skills in elderly people with satisfactory and lower cognitive function. Source: Medical News Today � 2010 MediLexicon International Ltd (19/03/10)

Sativex For MS Regulatory Update

Thu, 18 Mar 2010 07:23:00 EST

Sativex Regulatory Update - UK and Spanish regulators confirm no major issues outstanding. Regulatory process now at advanced stage. Approvals expected Q2 2010. GW Pharmaceuticals plc today provided an update on the progress of its regulatory submission for Sativex� Oromucosal Spray for the treatment of the symptoms of spasticity due to Multiple Sclerosis. The regulatory submission was filed in the UK and Spain under the European decentralised procedure in May 2009, with the UK acting as the Reference Member State. The regulatory process has now reached �Day 150� of the decentralised procedure and both the UK and Spanish regulators have concluded that there are no major quality, safety or efficacy issues remaining to be resolved. Resolution is now required only of points of clarification related to finalisation of wording on the patient information leaflet. We expect this document to be reviewed by the regulators in the coming weeks. Once the regulators have agreed final wording on the patient leaflet, the decentralised procedure can close and the process will enter its final phase. This final phase, known as the national phase, takes place separately in the UK and Spain and its purpose is to finalise local wording on product packaging and related documents. GW therefore expects regulatory approval in the UK and Spain during Q2 2010. Dr Stephen Wright, GW�s R&D Director, said, �This is a major milestone in the regulatory process for Sativex, and for GW�s future prospects. We look forward to working with the regulators towards a successful completion of this process and to supporting our marketing partners as they prepare for product launch. This progress with Sativex also provides further validation of GW�s cannabinoid platform and the significant long term promise of GW�s portfolio of cannabinoid medicines.� Sativex will be marketed in the UK by Bayer Schering Pharma, and in the rest of the European Union by Almirall S.A. Upon UK regulatory approval, GW expects to receive a �10m milestone payment from Bayer. A further �2.5m milestone payment is payable by Almirall following both regulatory and pricing approval in Spain. Following approval in the UK and Spain, submissions for approval will made in additional European countries during 2010 under the mutual recognition procedure. Source: GW Pharamceuticals (18/03/10)

Ibudilast in relapsing-remitting multiple sclerosis. A neuroprotectant?

Wed, 17 Mar 2010 10:53:00 EST

BACKGROUND: Ibudilast is a phosphodiesterase inhibitor influencing inflammation and neurodegeneration in multiple sclerosis (MS). This study evaluated the safety, tolerability, and effects on MRI parameters of 2 different doses of ibudilast in relapsing forms of MS. METHODS: In this multicenter, double-blind, phase 2 trial, patients with relapsing MS and gadolinium-enhancing lesions were randomly assigned 1:1:1 to receive 30 or 60 mg ibudilast or placebo every day for 12 months. The primary endpoint was the cumulative number of newly active lesions on bimonthly brain MRI over 12 months. Secondary endpoints included relapse rate, change in Expanded Disability Status Scale (EDSS) score, T2-hyperintense and T1-hypointense lesion volumes, and percent brain volume change (PBVC). RESULTS: A total of 297 patients were randomized in 19 centers. During the first 12 months, the mean number of active lesions and relapse rate did not differ between treatment arms. A reduction in PBVC (p = 0.04) was found in the 60-mg group (0.8%) compared with placebo (1.2%). Post hoc analysis showed a reduction in the proportion active lesions that evolved into persistent black holes for the 60-mg (0.14; p = 0.004) and 30-mg (0.17; p = 0.036) groups compared with the placebo group (0.24). Over 2 years, there were fewer patients (p = 0.026) with confirmed progression on the EDSS. Treatment with ibudilast was generally safe and well tolerated. CONCLUSION: Ibudilast showed no beneficial effect on the rate of newly active lesions and relapses. However, preliminary evidence suggests that ibudilast seems to act in a neuroprotective fashion as measured by 2 independent MRI outcomes, with a possible beneficial clinical effect on disability progression. Classification of evidence: This interventional study provides Class III evidence on the effect of ibudilast on disease activity. Barkhof F, Hulst HE, Drulovic J, Uitdehaag BM, Matsuda K, Landin R; For the MN166-001 Investigators. From the Image Analysis Center (F.B., H.E.H.) and MS Centre (B.M.J.U.), VU University Medical Center, Amsterdam, The Netherlands; Kliniki Centar Srbije (J.D.), Institut za Neurologiju Beograd, Serbia; and Medicinova Inc. (K.M., R.L.), San Diego, CA. Source: Pubmed PMID: 20200338 (17/03/10)

Absence of Epstein-Barr virus in the brain and CSF of patients with multiple sclerosis

Wed, 17 Mar 2010 05:27:00 EST

OBJECTIVE: Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that becomes latent in B-lymphocytes and has been implicated in the pathogenesis of multiple sclerosis (MS). We searched for latent and active EBV infection in MS brain and CSF. METHODS: Nested and non-nested real-time PCR were used to detect cell-specific and EBV-specific transcripts in 15 fresh-frozen and 5 formalin-fixed paraffin-embedded MS plaques and in single MS CSF B-lymphocytes and plasma cells. Intrathecal anti-EBV antibody synthesis was measured by ELISA. Immunocytochemistry was used to detect binding of MS CSF and recombinant antibodies (rAbs) generated from clonally expanded plasma cells in MS CSF to EBV-infected cells. RESULTS: No EBV RNA was found in MS CSF B-lymphocytes or plasma cells. In active MS plaques, EBV-encoded RNA (EBER)-1 was the only and rarely detected transcript. The frequency of detected intrathecal anti-EBV antibody synthesis in patients with MS did not differ from that in non-MS inflammatory CNS disease control patients. Anti-EBV antibodies were detected in the CSF of patients with MS, but MS rAbs did not react with EBV. CONCLUSIONS: Application of real-time PCR to multiple sclerosis brain and single B-lymphocytes in CSF did not reveal any evidence of active Epstein-Barr virus infection. Sargsyan SA, Shearer AJ, Ritchie AM, Burgoon MP, Anderson S, Hemmer B, Stadelmann C, Gattenl�hner S, Owens GP, Gilden D, Bennett JL. From the Departments of Neurology (S.A.S., A.J.S., A.M.R., M.P.B., S.A., G.P.O., D.G., J.L.B.), Microbiology (D.G.), and Ophthalmology (J.L.B.), University of Colorado Denver School of Medicine, Aurora; Department of Neurology (B.H.), Technische Universit�t, Munich; Universit�tsmedizin der Georg-August-Universit�t G�ttingen (C.S.), G�ttingen; and Department of Pathology (S.G.), Julius-Maximilians-University, W�rzburg, Germany. Source: Pubmed PMID: 20220124 (17/03/10)

Antiviral immune response in patients with multiple sclerosis and healthy siblings

Tue, 16 Mar 2010 10:50:00 EST

Summary The cause of MS is yet to be found. However, both environmental and genetic factors are believed to contribute to its pathogenesis. Amongst the environmental factors, viruses seem to play an important role. The authors of this article suggest that the nature of the immune response to Epstein-Barr virus is associated with the risk of developing MS. Mult Scler. 2010 Mar;16(3):355-8 Details The objective of this study was to determine the immune responses to candidate viral triggers of multiple sclerosis in patients and healthy siblings raised in the same family household. Virus antigen-specific IgG responses to Epstein-Barr virus-derived gene products as well as to human herpersvirus-6, human cytomegalovirus, and measles virus were evaluated in 25 multiple sclerosis patients and compared with 49 healthy full-siblings. IgG responses to the latent Epstein-Barr virus-encoded nuclear antigen-1 (EBNA1) were selectively increased in individuals with multiple sclerosis compared with their unaffected siblings. We conclude that elevated IgG responses towards EBNA1 are associated with the development of multiple sclerosis. Source: MS Society of Canada (16/03/10)

Advanced multiple sclerosis and the psychosocial impact on families

Mon, 15 Mar 2010 12:35:00 EST

This study explores family relationships and support needs when adapting to a relative's advanced-multiple sclerosis (MS) around transition into care. A multi-site qualitative study of relatives of people with advanced-MS was conducted. A purposive sample of 25 relatives was selected and interviewed either in the care home or participants' homes. Interviews were recorded, transcribed and analysed using grounded theory methodology and Atlas.ti 5.2 software. Data quality enhancement involved: a self-report questionnaire; triangulation and member-checking. Themes derived from the data were: information, communication and understanding; family relationships, roles and responsibilities; emotions, coping and support; life outlook and reflection. Provision of information and support for families around the transition into care appears to be inconsistent despite there being a need for family members to ask questions and discuss the impact of the condition. Relatives reported that as a family and as individuals they faced significant challenges and were in great need of support at times, but reflected that they would have found it very difficult to accept. Relatives were also often unsure what type of support would have helped. For care providers, there needs to be a shift from the traditional health care professional 'patient-centred' mindset towards more proactive family-centred approaches and steps to encourage this are articulated. Bowen C, Maclehose A, Beaumont JG. The Institute for Neuropalliative Rehabilitation, Royal Hospital for Neuro-disability, London SW15 3SW, UK. Source: Pubmed PMID: 20204981 (15/03/10)

Advanced MRI may speed diagnosis of multiple sclerosis

Mon, 15 Mar 2010 07:44:00 EST

MRI has become central to the diagnosis of multiple sclerosis, a complex disease of the central nervous system that affects over 400,000 people in Europe. Around 90% of all MS diagnoses are now based on MRI findings, owing to the modality�s high sensitivity to inflammation and demyelinating plaques. Trials have shown that an early diagnosis can make a big difference to the efficacy of MS drug treatments. Familiarity with the optimum diagnostic strategy is consequently crucial. Work is also under way to identify imaging biomarkers that could show whether a selected treatment is working, well before that same conclusion can be drawn from clinical findings. Members of the European Magnetic Imaging in Multiple Sclerosis (MAGNIMS) network shared with ECR delegates their expertise on MS diagnosis and management. The state-of-the-art session included practical tips for general radiologists who are faced with a potential case of MS, as well as details about research that will appeal to specialists in neuroradiology. �From a practical point of view, the most important message is to be familiar with the diagnostic criteria,� said Dr. Alex Rovira, head of the MRI unit at the Vall d�Hebron University Hospital, Barcelona, Spain, and the session chair. �In most European countries, the criteria required to start treatment for MS is to establish the diagnosis, and this is done with MRI. To avoid a wrong diagnosis, we have to know about the typical features of this disease and how we should apply imaging criteria.� An imaging-led diagnosis of MS is typically based on conventional MRI techniques. T2-weighted imaging can reveal lesions that indicate the presence of inflammation, demyelination, gliosis, axonal loss, and even remyelination. This information may be used by radiologists to estimate the overall burden of MS disease. Contrast-enhanced T1-weighted MRI can also be used to detect lesions that are currently active. A firm diagnosis is not usually made until the disease has been identified clinically in a separate part of the central nervous system some time after the initial onset of symptoms. It may take a couple of years for this criterion to be met. Repeated MRI, on the other hand, may identify new �silent� lesions and speed up the diagnosis. Alternatively, and of equal importance, imaging may be able to exclude MS and identify another cause of the patient�s symptoms. Once the diagnosis has been made, the value of MRI to MS patients begins to waver. Radiologists would like to use MRI to track progression of the disease, and perhaps even forecast periods of remission and relapse, but it is difficult to predict the outcome of treatment based on conventional MRI findings alone. What you see on imaging does not necessarily reflect what benefit the patient will get. The main reason for this clinical-radiological paradox is the complexity of MS. A number of factors contribute to disease severity, and not all of this information can be captured from T2- and T1-weighted imaging alone. Conventional MRI techniques may be able to spot MS lesions, but they say little about changes occurring within those lesions or about damage to brain tissue that has a �normal� appearance. More sophisticated techniques, such as MR spectroscopy (MRS), diffusion tensor imaging (DTI), and functional MRI (fMRI) are needed to complete the picture. �MS is not just focal inflammatory demyelination, as we used to think. There are a lot of additional things going on,� said Prof. Massimo Filippi, director of the Neuroimaging Research Unit at San Raffaele University in Milan, and one of the session�s three invited speakers. �It is a more complex puzzle that we still need to define.� This process would be aided if the application of these nonconventional MRI techniques could be standardized, according to Filippi. Clear criteria for the diagnosis of MS based on conventional MRI approaches have already been established, but as yet, there is no common language covering MRS, DTI, and/or fMRI findings. Nonconventional MRI techniques are becoming increasingly important in preclinical and clinical trials as companies move forward in developing neuroprotective drugs, as well as anti-inflammatory agents. The development of internationally acceptable guidelines relating to MRI-based monitoring of MS would help researchers from different institutions to compare their results. �We are lucky to have MRI, which is not a single technique but a set of techniques. We should not be using the same technique in all scenarios, but tailoring our approach to MRI when addressing different research questions,� Filippi said. Source: DiagnosticImaging.com � 1996 - 2010 UBM Medica LLC (15/03/10)

Standardized cannabis in Multiple Sclerosis: A case report

Fri, 12 Mar 2010 04:23:00 EST

Abstract A 52 year old female suffering from severe progressive multiple sclerosis was administered quantifiable amounts of standardized cannabis and monitored over the period of one year, while providing daily pain charts and records of her condition. An average daily intake of 500 mg of Tetrahydrocannabinol as cannabis was required to achieve a desired quality of life. Introduction Multiple Sclerosis (MS) is a difficult disease both to diagnose and to treat. Diagnosis often requires multiple visits to the physician and it may take years before MS is diagnosed, typed and treated. There is no cure for MS. Treatment is based on powerful immune system suppressants, mainly steroids and various types of Interferon, although others may be used as well. In addition, many types of medications including anticholinergics, antispasmodics, benzodiazepines and opiates are used to manage the muscle spasms, bladder incontinence issues and nerve pain that may be associated with MS. They do however prevent recurrence and slow progression of the illness. Prevention of MS through vitamin D supplementation is an intriguing possibility. In the study described here we trace the cannabis use of an MS patient over the course of one year. High Pressure Liquid Chromatography (HPLC) was performed to quantify cannabis. The subject made significant improvement with better pain control, decreased muscle spasms and general quality of life. The case described here is one of many observed at the Green Cross Society of B.C. Case Presentation The subject in this study, a 52-year-old female, is a member of the Green Cross Society which is a non-profit, organization, dedicated to supplying quality controlled, standardized cannabis to its qualified members. The participant involved in this year-long study was chosen primarily because she had an attentive, full-time, caregiver, who had tracked her illness since its beginning in the late 1970's. It was the caregiver that first noticed that cannabis was beneficial in relieving her symptoms. This however, was sometime after the disease was diagnosed. Initially she was subjected to a 10-day regimen of ACTH, plus various muscle relaxants and anxiolytics. Intermittent ACTH treatment occurred until 1985 when Magnetic Resonance Imaging confirmed her diagnosis with MS. She then began daily injections of Copaxone, which gave benefits including reduction of muscle spasms and a degree of pain management. In addition, she would also smoke cannabis to further alleviate symptoms. Initial symptoms had included numbness of the right side of the lip, and a depressed gag reflex that made swallowing difficult. These symptoms had been present for a decade prior to the suspicion and diagnosis of MS. In 1983, she began experiencing extreme pain in her lower lumbar region that radiated to her left foot, affecting her ability to walk. When she first came to the Society in 2007, she complained of chronic pain, tremor, difficulty in walking and a severe constant pain in her left foot. Through the Green Cross Society, the subject received advice on the best cannabis strain selection for her symptoms plus options on means of administration and dosage regimens. For the following year she ingested cannabis that had been tested for concentrations of the most abundant cannabinoids including Delta-9 Tetrahydrocannabinol (THC), Cannabidiol (CBD) and Cannabinol (CBN). Her caregiver provided daily (email) pain charts, plus ingested medications, and a description of the subject's general well being throughout the study. Discussion Results were assessed through daily dialogue with the subject's caregiver, review of accumulated pain charts, plus the subject's testimony. An almost immediate improvement was seen in the patient's condition when she began administering the standardized oral preparations. Pain scores were reduced from an 8�10 to 1�2 over the period of the first month during which time the optimal dosing regimen was established. Greatest benefit for pain and tremor was achieved consuming 6�8, 50 mg capsules per day, dosing at 4-hour intervals. The subject also consumed an average of 4�6 cannabis cigarettes per day, for breakthrough pain and/or mood enhancement. Measurement of the mean THC concentration of these cigarettes was 172 � 26 n = 30, that would equate to a dosage of 25 mg of THC per cigarette (0.5 grams per cigarette with roughly 70% loss to atmosphere),[1] adding another 125 mg to her daily consumption, totaling between 400 and 500 mg per day of THC. The average relative amounts of CBD and CBN are roughly 3% of that found for THC. A significant improvement in pain levels, tremor and general well being were observed. Functionally, the patient went from a state of virtual incapacitation to one where she can dress, go for walks and do some gardening: a dramatic improvement over the course of one year. The presence of CBD and CBN, although claiming no psychoactive effect, appear to modulate the binding of THC to its receptor and thus alter the efficacy of the preparation. The relative ratio of these three cannabinoids is determined by the specific strain of cannabis. Over the course of the study year it was found that the subject experienced optimal relief with strains containing relatively high CBD to THC ratio of 4�6%, a high THC concentration and relatively low CBN amount. Observations made with the study subject and, indeed, verified day-to-day at the Society is that those managing chronic pain prefer these ratios. The seemingly high amounts of THC (approximately 500 mg/day) required by the subject to manage her symptoms are often observed with persons of her genealogy (Scottish). An earlier publication on the effects of standardized cannabis and chronic pain management describes a similar tolerant response.[2] A phenomenon often witnessed at the Society is persons with Celtic genealogy require 3�5 five times greater dosage than those of Middle European or other descent. The only observed unwanted side effects were seen when the strain used in the oral capsules was changed to one that did not provide the same pain or anti-tremor relief as the strain provided at an earlier time. Simply put, there was some discomfort experienced in changing strains. Since the subject was receiving the medication by mail, from time to time, she would run out of the oral preparation at which time her symptoms would worsen to their pre-regimen state within days. Recent tests of liver functions proved normal. Conclusions The established non-toxicity of cannabis and non-addictive properties[3] make it an excellent candidate for treating the symptoms of numerous illnesses. The case described here is one of many observed at the Green Cross Society of B.C. Abbreviations CBD-A: Cannabidiolic acid; CBD: Cannabidiol; CBN-A: Cannabinolic Acid; CBN: Cannabinol; THC-A: Tetrahydrocannabinolic Acid; THC: Delta-9 tetrahydrocannabinol; THF: tetrahydrofuran; HPLC: high performance liquid chromatography. Consent Written informed consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests The authors declare that they have no competing interests. Authors' contributions PH conducted data collection and analysis, plus manuscript draft preparation. MS, interpreted data and edited the manuscript. Acknowledgements The authors would like to thank the membership of the Green Cross Society for their unwavering support and help through all the studies conducted last year. Cases J. 2010;3:7 � 2010 Cases Network, Ltd. Source: Medscape from WebMD � 1994-2010 by WebMD LLC. (12/03/10)

Vitamin D 'triggers and arms' the immune system

Mon, 08 Mar 2010 05:14:00 EST

The so-called sunshine vitamin, which can be obtained from food or manufactured by human skin exposed to the sun, plays a key role in boosting the immune system, researchers believe. In particular it triggers and arms the body's T cells, the cells in the body that seek out and destroy any invading bacteria and viruses. Scientists at the University of Copenhagen have discovered that Vitamin D is crucial to activating our immune defences and that without sufficient intake of the vitamin, the killer cells of the immune system � T cells � will not be able to react to and fight off serious infections in the body. For T cells to detect and kill foreign pathogens such as clumps of bacteria or viruses, the cells must first be �triggered� into action and "transform" from inactive and harmless immune cells into killer cells that are primed to seek out and destroy all traces of invaders. The researchers found that the T cells rely on vitamin D in order activate and they would remain dormant, �na�ve� to the possibility of threat if vitamin D is lacking in the blood. Professor Carsten Geisler from the Department of International Health, Immunology and Microbiology, said: "When a T cell is exposed to a foreign pathogen, it extends a signalling device or �antenna� known as a vitamin D receptor, with which it searches for vitamin D. "This means that the T cell must have vitamin D or activation of the cell will cease. If the T cells cannot find enough vitamin D in the blood, they won�t even begin to mobilise. � The discovery, the scientists believe, provides much needed information about the immune system and will help them regulate the immune response. This is important not only in fighting disease but also in dealing with anti-immune reactions of the body and the rejection of transplanted organs. Active T cells multiply at an explosive rate and can create an inflammatory environment with serious consequences for the body. After organ transplants, T cells can attack the donor organ as a �foreign invader�. In autoimmune diseases, like arthritis or Crohns Disease, T cells mistake fragments of the body�s own cells for foreign invaders, leading to the body launching an attack upon itself. For the research team, identifying the role of vitamin D in the activation of T cells has been a major breakthrough. �Scientists have known for a long time that vitamin D is important for calcium absorption and the vitamin has also been implicated in diseases such as cancer and multiple sclerosis, but what we didn�t realise is how crucial vitamin D is for actually activating the immune system � which we know now, � said the researchers. The findings, continues Professor Geisler, �could help us to contain infectious diseases and global epidemics. They will be of particular use when developing new vaccines, which work precisely on the basis of both training our immune systems to react and suppressing the body�s natural defences in situations where this is important � as is the case with organ transplants and autoimmune disease.� Most Vitamin D is produced as a natural by-product of the skin�s exposure to sunlight. It can also be found in fish liver oil, eggs and fatty fish such as salmon, herring and mackerel or taken as a dietary supplement. The findings are published in the latest edition of Nature Immunology. Source: Telegraph.co.uk � Copyright of Telegraph Media Group Limited 2010 (08/03/10)

Researchers find further evidence linking Epstein-Barr virus and risk of multiple sclerosis

Fri, 05 Mar 2010 03:11:00 EST

Researchers from the Harvard School of Public Health, Walter Reed Army Institute of Research, and a team of collaborators have observed for the first time that the risk of multiple sclerosis (MS) increases by many folds following infection with the Epstein-Barr virus (EBV). This finding implicates EBV as a contributory cause to multiple sclerosis. The study appears in an advance online edition of the journal Annals of Neurology and will appear in a later print edition. Hundred of thousands of individuals not infected with EBV were followed up for several years through repeated blood samples collections. Researchers were then able to determine the time when individuals developed an EBV infection and its relation to MS onset. "The recruitment of individuals before they were infected with EBV and following up with them for several years is the critical methodological aspect that makes this study qualitatively different from all previous work," said Alberto Ascherio, senior author of the study and professor of epidemiology and nutrition at Harvard School of Public Health and professor of medicine at Harvard Medical School. MS is a chronic degenerative disease of the central nervous system. Women are more likely than men to get the disease and it is the most common neurologically disabling disease in young adults. Although genetic predisposition plays an important role in determining susceptibility, past studies have shown that environmental factors are equally important. EBV is a herpes virus and one of the most common human viruses worldwide. Infection in early childhood is common and usually asymptomatic. Late age at infection, however, often causes infectious mononucleosis. In the U.S., upwards of 95% of adults are infected with the virus, but free of symptoms. EBV has been associated with some types of cancer and can cause serious complications when the immune system is suppressed, for example, in transplant recipients. There is no effective treatment for EBV. This is the first study based on the longitudinal follow-up of several thousand individuals who were not infected with EBV at the time of recruitment. The study population was made up of active-duty US Army, Navy, and Marines personnel who have at least one blood sample in the Department of Defense Serum Repository. The electronic databases of the Physical Disability Agencies of the US Army and Navy were then searched for individuals whose records indicated a possible diagnosis of MS reported between 1992 and 2004. The researchers selected 305 individuals diagnosed with MS and who had blood specimens collected before the date of their diagnosis. Two controls for each case were then selected from the serum database and matched by branch of service, sex, date of blood collection, and age at time of blood collection. The study found that MS risk is extremely low among individuals not infected with EBV, but it increases sharply in the same individuals following EBV infection. "The observation that MS occurred only after EBV is a big step forward," said Alberto Ascherio. "Until now we knew that virtually all MS patients are infected with EBV, but we could not exclude two non-causal explanations for this finding: that EBV infection is a consequence rather than a cause of MS, and that individuals who are EBV negative could be genetically resistant to MS. Both of these explanations are inconsistent with the present findings," said Ascherio. "The evidence is now sufficiently compelling to justify the allocation of more resources to the development of interventions targeting EBV infection, or the immune response to EBV infection, as these may contribute to MS prevention," he said. The study was supported by a grant from the National Institute of Neurological Disorders and Stroke. "Primary Infection with the Epstein-Barr Virus and Risk of Multiple Sclerosis," Lynn I. Levin, Kassandra L. Munger, Eilis J. O'Reilly, Kerstin I. Falk, Alberto Ascherio, Annals of Neurology, online January 20, 2010 Source: ScienceBlog Copyright, Science Blog 2010. (05/03/10)

Atorvastatin Combined To Interferon to Verify the Efficacy (ACTIVE) in relapsing-remitting active multiple sclerosis patients: a longitudinal controlled trial of combination therapy

Tue, 02 Mar 2010 03:37:00 EST

Summary Interferon beta (IFNb) is a first-line treatment for people with MS, but its efficacy may vary amongst different people. Statins are known to have anti-inflammatory properties. In this unicentre controlled clinical trial carried out with 45 participants, the authors aimed to assess safety, tolerability and efficacy of low-dose atorvastatin, which belongs to the group of statins, plus subcutaneous IFNb-1a (Rebif44�), given for 24 months, in people with MS responding poorly to interferon beta-1a. The people that received the combined therapy (atorvastatin plus IFNb-1a) had better outcome than those that received IFNb-1a alone, in terms of active inflammatory lesions in the MRI, relapses, and risk of increasing disability. The authors have concluded that low-dose atorvastatin may be beneficial, as add-on therapy, in poor responders to high-dose interferon beta-1a alone. Details A large body of evidence suggests that, besides their cholesterol-lowering effect, statins exert anti-inflammatory action. Consequently, statins may have therapeutic potential in immune-mediated disorders such as multiple sclerosis. The objectives were to determine safety, tolerability and efficacy of low-dose atorvastatin plus high-dose interferon beta-1a in multiple sclerosis patients responding poorly to interferon beta-1a alone. Relapsing-Remitting multiple sclerosis patients, aged 18-50 years, with contrast-enhanced lesions or relapses while on therapy with interferon beta-1a 44 microg (three times weekly) for 12 months, were randomized to combination therapy (interferon + atorvastatin 20 mg per day; group A) or interferon alone (group B) for 24 months. Patients underwent blood analysis and clinical assessment with the Expanded Disability Status Scale every 3 months, and brain gadolinium-enhanced magnetic resonance imaging at screening, and 12 and 24 months thereafter. Primary outcome measure was contrast-enhanced lesion number. Secondary outcome measures were number of relapses, EDSS variation and safety laboratory data. Forty-five patients were randomized to group A (n = 21) or B (n = 24). At 24 months, group A had significantly fewer contrast-enhanced lesions versus baseline (p = 0.007) and significantly fewer relapses versus the two pre-randomization years (p < 0.001). At survival analysis, the risk for a 1-point EDSS increase was slightly higher in group B than in group A (p = 0.053). Low-dose atorvastatin may be beneficial, as add-on therapy, in poor responders to high-dose interferon beta-1a alone. Source: MS Society Of Canada (02/03/10)

Blood brain barrier compromise with endothelial inflammation may lead to autoimmune loss of myelin during multiple sclerosis

Mon, 01 Mar 2010 05:29:00 EST

Multiple sclerosis is an autoimmune disease characterized by multifocal areas of inflammation and demyelination within the central nervous system. The mechanism that triggers the disease remains elusive. However, recent findings may indicate that multiple sclerosis, at its source, could be a hemodynamic disorder. It has been found that multiple sclerosis patients exhibit significant stenoses in extracranial veins draining the central nervous system (in azygous and internal jugular veins), which are associated with significant pressure gradients measured across strictures. Such anatomic venous abnormalities were not found in the control group of healthy subjects. In this review, it is hypothesized that pathological refluxing venous flow in the cerebral and spinal veins increases the expression of adhesion molecules, particularly intercellular adhesion molecule-1 (ICAM-1), by the cerebrovascular endothelium. This, in turn, could lead to the increased permeability of the blood-brain barrier. Inflamed and activated endothelium could secrete proinflammatory cytokines, including GM-CSF and TGF-beta In these settings, monocytes could transform into antigen-presenting cells and initiate an autoimmune attack against myelin-containing cells. Consequently, a potential therapeutic option for multiple sclerosis could be pharmacotherapy with either substances that strengthen the tight-junctions barrier, or with agents that reduce the expression of adhesion molecules. In addition, surgical correction could be an option in some anatomical variants of pathologic venous outflow. We are optimistic that a hemodynamic approach to the multiple sclerosis pathogenesis can open a new chapter of investigations and treatment of this debilitating neurologic disease. Simka M. Department of Angiology, Private Healthcare Institution SANA, Pszczyna, Poland. Source: PMID: 19442163 (01/03/10)

Iron leads to memory impairment that is associated with a decrease in acetylcholinesterase pathways

Mon, 01 Mar 2010 04:34:00 EST

Perez VP, de Lima MN, da Silva RS, Dornelles AS, Vedana G, Bogo MR, Bonan CD, Schr�der N. Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, Av. Ipiranga, 6681 Pr�dio 12C, Sala 340, 90619-900 Porto Alegre, RS, Brazil. Increasing evidence indicates that excessive iron in selective regions of the brain may be involved in the etiology of neurodegenerative disorders. Accordingly, increased levels of iron have been described in brain regions of patients in Parkinson's and Alzheimer's diseases. We have characterized neonatal iron loading in rodents as a novel experimental model that mimics the brain iron accumulation observed in patients with neurodegenerative diseases and produces severe cognitive impairment in the adulthood. In the present study we have investigated the involvement of the cholinergic system on iron-induced memory impairment. The effects of a single administration of the acetylcholinesterase (AChE) inhibitor galantamine or the muscarinic receptor agonist oxotremorine on iron-induced memory deficits in rats were examined. Male Wistar rats received vehicle or iron (10.0 mg/kg) orally at postnatal days 12 to 14. At the age of 2-3 months, animals were trained in a novel object recognition task. Iron-treated rats showed long-term impairments in recognition memory. The impairing effect was reversed by systemic administration of galantamine (1 mg/kg) immediately after training. In addition, iron-treated rats that received oxotremorine (0.5 mg/kg) showed enhanced memory retention. Rats given iron showed a decreased AChE activity in the striatum when compared to controls. The results suggest that, at least in part, iron-induced cognitive deficits are related to a dysfunction of cholinergic neural transmission in the brain. These findings might have implications for the development of novel therapeutic strategies aimed at ameliorating cognitive decline associated with neurodegenerative disorders. Source: Pubmed PMID: 20158466 (01/03/10)

The severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis is related to altered cerebrospinal fluid dynamics

Sun, 28 Feb 2010 04:18:00 EST

Chronic cerebrospinal venous insufficiency(CCSVI) is a vascular picture that shows a strong association with multiple sclerosis (MS). The aim of this study was to investigate the relationship between a Doppler cerebral venous hemodynamic insufficiency severity score (VHISS) and cerebrospinal fluid (CSF) flow dynamics in 16 patients presenting with CCSVI and relapsing-remitting MS (CCSVI-MS) and in eight healthy controls (HCs). The two groups (patients and controls) were evaluated using validated echo-Doppler and advanced 3T-MRI CSF flow measures. Compared with the HCs, the CCSVI-MS patients showed a significantly lower net CSF flow (p=0.027) which was highly associated with the VHISS (r=0.8280, r2=0.6855; p=0.0001). This study demonstrates that venous outflow disturbances in the form of CCSVI significantly impact on CSF pathophysiology in patients with MS. Zamboni P, Menegatti E, Weinstock-Guttman B, Schirda C, Cox JL, Malagoni AM, Hojanacki D, Kennedy C, Carl E, Dwyer MG, Bergsland N, Galeotti R, Hussein S, Bartolomei I, Salvi F, Zivadinov R. Source: Pubmed PMID: 20018140 (28/02/10)

Italian researchers discover a possible onset mechanism for Multiple Sclerosis

Fri, 26 Feb 2010 05:46:00 EST

A non-pathogenic bacterium is capable to trigger an autoimmune disease similar to the multiple sclerosis in the mouse, the model animal which helps to explain how human diseases work. This is what a group of researchers from the Catholic University of Rome, led by Francesco Ria (Institute of General Pathology) and Giovanni Delogu (Institute of Microbiology), have explained for the first time in a recently published article on the Journal of Immunology. Multiple sclerosis is a disease due to an inflammatory reaction provoked by the immune system. It causes the disruption of the coating of the nerve fibres in the Central Nervous System. "We do not know what causes multiple sclerosis", explains Francesco Ria, immunologist of the Catholic University. "We know that there exist a genetic factor and an environmental factor, but we do not yet posses a satisfactory theory which can explain how exactly this environmental factor works". Currently, there are two competing theories on the field: according to a first hypothesis, a virus hides within the brain and what causes the disease is the immunologic antiviral reaction. On the other hand, the second hypothesis states that a viral or bacterial pathogen similar to specific molecules of the Central Nervous System causes an inflammation which provokes a reaction of the immune system. This reaction ends up destroying the brain cells. The latter is called the autoimmune hypothesis. This is the hypothesis that the researchers coming from the Institutes of General Pathology, Microbiology and Anatomy of the Catholic University of Rome have been testing with their two-year long work. To demonstrate the viability of this idea, scientists have fooled the mouse immune system, modifying subtly a bacterium of the common family of mycobacteria (the same family to which also the bacterium causing tuberculosis belongs) to make it look like to myelin, the protein coating nerve cells. This modified mycobacterium is completely innocuous. As all external agents, though, it is capable to trigger the reaction of the T-cells of the immune systems. They intervene to destroy it. Since they are innocuous bacteria, although very common in the environment, and since they induce an immune reaction, they are the ideal bacteria scientists can use to study the environmental factor contributing, together with the genetic factor, to cause multiple sclerosis. "Normally, T-cells cannot penetrate into the Central Nervous System", adds Rea, "because the hematoencephalic barrier prevents them from doing so. But the bacterium modifies the characteristics of the T-cells and allows them to overcome the barrier. In 15 days the bacterium disappears completely from the body". Yet these T-cells can now enter into the brain. This way, they begin to attack the myelin of the nerve cells, and here is how the immune disease breaks out. "We basically demonstrate � explains Rea � that in an animal model it is possible to be infected with something not carrying any disease, and later on develop a purely autoimmune disease". Yet there is another element in this complex research, sponsored by the Italian Association of Multiple Sclerosis (AISM). "Normally � clarifies Rea � to understand which diseases we have encountered, we measure the antibodies produced by that specific pathogen. But there is a whole world of infectious agents which do not induce the production of antibodies, as is the case in our research: mycobacteria and many other bacteria produce a very low and variable number of antibodies. It is thus very hard to establish whether a population has encountered that specific infectious agent. So, we demonstrate that those infectious agents which are more likely to produce an autoimmune reaction are just those which do not induce antibody production". Obviously, this is only the first step to better understand the way this very complex and devastating disease works. Ria and Delogu are not stopping here: "We want to try to understand the exact characteristics which this infectious agent should have", they explain. "Might it truly be a good experimental model for multiple sclerosis? If we had prolonged the action of the bacteria, would we have favoured or hampered the development of the disease? And what about the myelin-like bacterium protein: where should it lie? On the surface, or inside? These are all questions � conclude the two researchers � which we will be trying to answer in the next years, in the hope to defeat this terrible illness. We could even imagine to develop a vaccine by which we could prevent the immune response associated to multiple sclerosis". Source Eureka Alert! (26/02/10)

Copaxone(R) 15-year study in Multiple Sclerosis patients demonstrates robust long-term efficacy and safety

Thu, 25 Feb 2010 10:43:00 EST

Teva Pharmaceutical Industries Ltd. announced the publication of data from the 15-year clinical study with Copaxone(R) (glatiramer acetate injection), which is the longest prospective and continuous evaluation ever conducted in relapsing-remitting multiple sclerosis (RRMS) patients. The data were published in the February issue of the journal Multiple Sclerosis. The 15-year clinical study demonstrated that more than 80 percent of patients were still walking without assistance despite a mean MS disease duration of 22 years, and two-thirds of patients have not transitioned to secondary progressive MS. Patients who remained in the study over a mean of 15 years showed a reduction in annualized relapse rate (ARR) from baseline as well as minimal increase in Expanded Disability Status Scale (EDSS). On average, the ARR in the ongoing cohort declined from 1.12 � 0.82 to 0.25 � 0.34 at the 15-year analysis. Additionally, the study reinforces the established long-term safety profile associated with Copaxone(R). The most common adverse events associated with Copaxone(R) were local injection-site reactions and immediate post-injection reactions. No other immune-mediated disorders, infections or malignancies were reported. "This study is important for the MS community as it further confirms the benefits of continuous long-term use of Copaxone(R) and its ability to effectively slow the natural progression of this disease," said Corey Ford, M.D., Ph.D., primary investigator in the study and Professor of Neurology, Director of the Multiple Sclerosis Specialty Clinic and Assistant Dean for Research at the University of New Mexico Health Sciences Center. "It is encouraging to see such long-term results that further support the well-established benefit-to-risk profile of this treatment relevant to a life-long disease." "We are pleased to see that results from this study reinforce the long term efficacy and safety of Copaxone(R)," said Moshe Manor, Teva's Group Vice President, Global Branded Products. "The longest term study extension further demonstrates Teva's investment in Copaxone(R) and our ongoing commitment to improve the disease course of MS." This study represents the only prospective, open-label follow-up study designed to evaluate continuous immunomodulatory therapy in RRMS patients. The study, currently in its 19th year, was extended to 20 years based on the positive results seen thus far and the interest of the MS community in the long term outcomes of treatments for this life-long disease. About the Study The study "Continuous Long-Term Immunomodulatory Therapy in Relapsing Multiple Sclerosis: Results from the 15-Year Analysis of the U.S. Prospective Open-label Study of Glatiramer Acetate," a follow-up to the pivotal, Phase III trial, followed 100 ongoing Copaxone(R) (glatiramer acetate injection) patients starting in 1991. Patients' EDSS scores were evaluated every six months. Confirmed disability progression was defined as greater-than or equal to 1.0 EDSS point increase sustained for six months. Patients were classified as "stable/improved" if EDSS score changes were less or equal to 0.5 points. Proportions of patients who reached confirmed thresholds of EDSS 4, 6, or 8 while on Copaxone(R), and Kaplan-Meier (KM) estimates of median times to these thresholds, were obtained. Fifty-seven percent of patients experienced either stabilized or improved EDSS scores, while 65 percent has not yet transitioned to Secondary-Progressive Multiple Sclerosis (SPMS). While being treated with Copaxone(R), the mITT patients' ARR declined from 1.18+/-0.82 to 0.43+/-0.58/year. Source: Teva Pharmaceutical Industries Ltd. (25/02/10)

Genome-wide association study in a high-risk isolate for Multiple Sclerosis reveals associated variants in STAT3 gene

Wed, 24 Feb 2010 04:44:00 EST

Genetic risk for multiple sclerosis (MS) is thought to involve both common and rare risk alleles. Recent GWAS and subsequent meta-analysis have established the critical role of the HLA locus and identified new common variants associated to MS. These variants have small odds ratios (ORs) and explain only a fraction of the genetic risk. To expose potentially rare, high-impact alleles, we conducted a GWAS of 68 distantly related cases and 136 controls from a high-risk internal isolate of Finland with increased prevalence and familial occurrence of MS. The top 27 loci with p < 10(-4) were tested in 711 cases and 1029 controls from Finland, and the top two findings were validated in 3859 cases and 9110 controls from more heterogeneous populations. SNP (rs744166) within the STAT3 gene was associated to MS (p = 2.75 x 10(-10), OR 0.87, confidence interval 0.83-0.91). The protective haplotype for MS in STAT3 is a risk allele for Crohn disease, implying that STAT3 represents a shared risk locus for at least two autoimmune diseases. This study also demonstrates the potential of special isolated populations in search for variants contributing to complex traits. Copyright � 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved. Jakkula E, Lepp� V, Sulonen AM, Varilo T, Kallio S, Kemppinen A, Purcell S, Koivisto K, Tienari P, Sumelahti ML, Elovaara I, Pirttil� T, Reunanen M, Aromaa A, Oturai AB, S�ndergaard HB, Harbo HF, Mero IL, Gabriel SB, Mirel DB, Hauser SL, Kappos L, Polman C, De Jager PL, Hafler DA, Daly MJ, Palotie A, Saarela J, Peltonen L. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00290, Finland; Unit of Public Health Genomics, National Institute for Health and Welfare, Helsinki 00271, Finland; Program in Medical and Population Genetics and Genetic Analysis Platform, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Source: Pubmed PMID: 20159113 (24/02/10)

Adeona announces completion of 50% enrollment in Trimesta(TM) Multiple Sclerosis clinical trial

Tue, 23 Feb 2010 09:45:00 EST

Adeona Pharmaceuticals, Inc. announced today that the clinical trial of its investigational drug Trimesta(TM) (estriol oral) being conducted by principal investigator Dr. Rhonda Voskuhl (Director, UCLA Multiple Sclerosis Program, UCLA Dept. of Neurology) has enrolled over 75 patients. The total planned enrollment is 150 patients. The Trimesta(TM) study is a double-blind, placebo-controlled clinical trial. Sixteen sites in the United States are currently enrolling patients. Investigators at these clinical sites are administering either Trimesta(TM) along with glatimer acetate (Copaxone(R)), an FDA approved therapy for multiple sclerosis, or a placebo plus glatimer acetate to women between the ages of 18 to 50 who have been recently diagnosed with relapsing-remitting multiple sclerosis. The primary endpoint is relapse rates at two years with a one year interim analysis using standard clinical measures of multiple sclerosis disability. Secondary endpoints of magnetic resonance imaging measurements of brain lesion and effects on cognition will also be studied. The Trimesta(TM) clinical trial has received a $5 million grant from the National Multiple Sclerosis Society in partnership with the National Multiple Sclerosis Society's Southern California chapter, with support from the National Institutes of Health. In January of 2010, it was announced that an additional $860,440 in grant funding had been received allowing the number of clinical sites enrolling patients for this study to more than double to 16 clinical sites. Trimesta(TM) has previously completed a 22-month, single-agent, crossover clinical trial in the United States for the treatment of relapsing remitting multiple sclerosis. The results showed the total volume and number of enhancing pathogenic myelin lesions (established neuroimaging measurements of disease activity in multiple sclerosis) decreased during the treatment period as compared to a six-month pretreatment baseline period. The median total enhancing lesion volumes decreased by 79 percent (p=0.02) and the number of lesions decreased by 82 percent (p=0.09) within the first three months of treatment with Trimesta(TM). "We are encouraged with the accelerated pace of patient enrollment in the Trimesta clinical trial," stated James S. Kuo, M.D., M.B.A., Adeona's Chairman and CEO. "Based on the previous clinical trial results, we are hopeful that we will see an improvement in cognition in multiple sclerosis patients. Such a clinical finding would serve a compelling clinical need in these patients and highly differentiate the product from others currently in development." Source: Adeona Pharmaceuticals, Inc. (23/02/10)

Low Dose Naltrexone(LDN) improves mental health quality of life in MS

Mon, 22 Feb 2010 11:38:00 EST

A rapid on-line publication of the first randomised controlled trial of low dose naltrexone in MS in the Annals of Neurology has been reported prior to hard copy publication. The study randomised 80 people with MS to receive LDN or placebo in a cross-over study where people took the LDN or placebo for eight weeks, then swapped to the other study drug. This appears to be the first drug trial in MS that was not funded by the pharmaceutical industry, but by the participants themselves. The researchers found significant improvements for LDN over placebo in several mental health quality of life measures. This appears to be the beginning of formal research into LDN in MS, and further trials are eagerly awaited by the research community. Download the full accepted pre-publication version of the paper. Source: Taking Control of Multiple Sclerosis (22/02/10)

Clinical effect of neutralizing antibodies to interferon beta that persist long after cessation of therapy for Multiple Sclerosis

Mon, 22 Feb 2010 06:06:00 EST

OBJECTIVES: To confirm that neutralizing antibodies (NAb) to interferon beta can persist after therapy withdrawal and to evaluate whether persisting NAb are associated with a worse clinical disease course in multiple sclerosis (MS). DESIGN: Retrospective study. SETTING: Tertiary referral center in the Netherlands. Patients A total of 71 patients with relapsing-remitting multiple sclerosis treated with interferon beta in the past. MAIN OUTCOME MEASURES: Persisting NAb after therapy withdrawal were tested using the cytopathic effect assay. Patients with and without persisting NAb were compared on several outcomes: the change in annualized relapse rate from prior to interferon beta treatment initiation to after cessation of treatment, time to sustained disability on the Kurtzke Expanded Disability Status Scale, and the use of disease-modifying treatments after cessation of treatment with interferon beta. RESULTS: Seventeen of 71 patients (24%) tested NAb positive after a median interval of 25 months (interquartile range, 10-51 months) after interferon beta treatment cessation. Eleven of these 17 patients (15%) were high-titer NAb positive (>150 10-fold reduction units per mL). Persisting NAb were associated with an increase in the annualized relapse rate (P = .04) and a reduction in time to reach a sustained Expanded Disability Status Scale score of 6.0, ie, the need for unilateral assistance to walk 100 m (P = .02). Moreover, NAb-positive patients were treated with second-line therapy significantly more often, especially mitoxantrone (P = .006). CONCLUSION: Anti-interferon beta NAb can persist after interferon beta treatment withdrawal and are associated with overt clinical disease activity. This is made apparent by an increase in relapse rate and faster disability progression and is supported by the observed need for more aggressive therapy after interferon beta treatment cessation. Prospective studies are warranted to confirm these results. Source: Pubmed PMID: 20142519 (22/02/10)

Novartis' Gilenia (FTY720) gets FDA priority review status

Mon, 22 Feb 2010 04:10:00 EST

Novartis AG pulled further ahead of rival Merck in the bid to get the first oral multiple sclerosis treatment to market after the Swiss drugmaker's Gilenia was given U.S. priority review status. Novartis's Gilenia, FTY720, is competing with Merck MGaA's pill cladribine against the debilitating nervous disease. U.S. regulators held up Merck's application to bring its cladribine drug to market in November. The German drugmaker met with U.S. regulators in January about the approval process but it does not yet have a clear resubmission timetable. The priority review for Gilenia, which cuts the standard review time to six months from 10, comes after the U.S. Food and Drug Administration accepted the regulatory submission made in December for the drug. Novartis said, however, the FDA could still extend its review at the end of the six month period in June as Gilenia involves a new active ingredient, meaning the FDA is likely to require an advisory committee meeting. The two treatments from Novartis and Merck are expected to take a sizable chunk of the $8.6 billion market for MS since they are easier to take than the injectables from Teva, Biogen Idec, Bayer and Merck KGaA itself that currently dominate. However both experimental drugs have serious side effects because they interfere with the body's immune system and the companies have to convince physicians and investors the balance of risk and benefit stacks up. MS can cause mild symptoms in some people and permanent disability in others. Symptoms may include numbness or weakness in one or more limbs, partial or complete loss of vision, tingling or pain, an electric-shock sensation with certain head movements, tremors and an unsteady gait. Source: Yahoo! News � 2010 Reuters Limited. (22/02/10)

Marijuana has therapeutic value for pain-related medical conditions such as Multiple Sclerosis

Sat, 20 Feb 2010 01:52:00 EST

Researchers from the University of California�s Center for Medicinal Cannabis Research (CMCR) have found �reasonable evidence that cannabis is a promising treatment� for some specific, pain-related medical conditions. Their findings, presented today to the California legislature and public, are included in a report available on the CMCR web site at http://www.cmcr.ucsd.edu. �We focused on illnesses where current medical treatment does not provide adequate relief or coverage of symptoms,� explained CMCR director, Igor Grant, MD, Executive Vice-Chair of the Department of Psychiatry at the UCSD School of Medicine. �These findings provide a strong, science-based context in which policy makers and the public can begin discussing the place of cannabis in medical care.� Researchers have completed five scientific clinical trials, with more in progress. These studies showed that cannabis can be helpful in easing pain in selected syndromes caused by injury or diseases of the nervous system and possibly for painful muscle spasms due to multiple sclerosis. �These scientists created an unparalleled program of systematic research, focused on science-based answers rather than political or social beliefs,� said Senator John Vasconcellos, original author of The Medical Marijuana Research Act of 1999 (SB847) which led to the creation of the CMCR. Study results have been published in high-impact medical journals, garnering national and international attention which prompted leading experts to come together and foster scientific dialog on the possible uses of cannabis as a therapeutic agent. More study will be necessary to figure out the mechanisms of action and the full therapeutic potential of cannabinoid compounds, according to the UC researchers. About The Center for Medicinal Cannabis Research The CMCR was created in 2000 (through the passage of SB847) to conduct clinical and pre-clinical trials of cannabinoids, including smoked marijuana, to provide evidence, one way or the other, to answer the question �Does marijuana have therapeutic value?� The program�s purpose is to oversee objective, high-quality, medical research that would enhance understanding of the efficacy and adverse effects of marijuana as a pharmacological agent. The project was never to be construed as encouraging or sanctioning the social or recreational use of marijuana. Source: University of California � 2010 UCSD Medical Center. (20/02/10)

Exercise has protective effect on brains of multiple sclerosis patients

Fri, 19 Feb 2010 05:17:00 EST

Exercise is good for the brains of patients with multiple sclerosis, a new study has found. In the new study, researchers found that highly fit multiple sclerosis patients performed significantly better on tests of cognitive function than similar less-fit patients. In addition, MRI scans of the patients showed that the fitter MS patients showed less damage in parts of the brain that show deterioration as a result of MS, as well as a greater volume of vital gray matter. �We found that aerobic fitness has a protective effect on parts of the brain that are most affected by multiple sclerosis,� said Ruchika Shaurya Prakash, lead author of the study and assistant professor of psychology at Ohio State University. �As a result, these fitter patients actually show better performance on tasks that measure processing speed.� The study, done with colleagues Robert Motl and Arthur Kramer of the University of Illinois and Erin Snook of the University of Massachusetts, Amherst, appears online in the journal Brain Research and will be published in a future print edition. The study involved 21 women diagnosed with relapsing-remitting MS. They were compared with 15 age- and education-matched healthy female controls. The study assessed fitness, cognitive function, and structural changes in all participants. Source: Health News Copyright� 2010 Taragana (19/02/10)

Migraine tied to raised Multiple Sclerosis risk

Wed, 17 Feb 2010 02:18:00 EST

Migraines are more common in women with multiple sclerosis (MS) than in those without the disease, new research shows. The study looked at close to 117,000 U.S. women participating in the Nurses� Health Study II, including 18,000 who had been diagnosed with migraine at the start of the study. The women were assessed every two years over a 16-year period. Of the 375 women who developed MS during the study, 82 had been diagnosed with migraine when the study began. The researchers determined that women with a migraine diagnosis at the start of the study were 47 percent more likely to develop MS than other women. The risk was the same regardless of age, vitamin D levels, body mass index, smoking status or where the women lived. This is the first large-scale study of its kind to examine the association between migraine and MS. The findings were released online Feb. 16 and are scheduled to be presented at the American Academy of Neurology�s annual meeting in Toronto in April. �While having a history of migraine diagnosis was linked to MS, women with migraine need to know that over 99 percent of them will never develop MS, thus having migraine should definitely not be a reason to worry about getting MS,� study author Dr. Ilya Kister, of the New York University School of Medicine, said in a news release from the American Academy of Neurology. �More research is needed since it�s still not known whether migraine is a risk factor for developing MS or if it is a condition that occurs at the same time as MS,� Kister added. Source: Health.com � 2010 Health Media Ventures, Inc (17/02/10)

Add-On Daclizumab (Zenapax) may reduce MS disease activity more than Interferon Beta alone

Tue, 16 Feb 2010 06:04:00 EST

Add-on daclizumab treatment might reduce multiple sclerosis disease activity more than standard interferon beta treatment alone, according to a study published online first and appearing in the April edition of The Lancet Neurology. Daclizumab has reduced multiple sclerosis disease activity in previous non-randomised studies. In the current study, John W. Rose, MD, Neurovirology Research Laboratory, VA Medical Center, Salt Lake City, Utah and colleagues aimed to assess whether daclizumab reduces disease activity in patients with active relapsing multiple sclerosis who are receiving standard interferon beta treatment. The international, multicentre, phase 2 study randomised 230 patients with active relapsing multiple sclerosis who were taking interferon beta to receive add-on subcutaneous daclizumab 2 mg/kg every 2 weeks (interferon beta and high-dose daclizumab group; n = 75), daclizumab 1 mg/kg every 4 weeks (interferon beta and low-dose daclizumab group; n = 78), or interferon beta and placebo for 24 weeks (n = 77). The primary endpoint was total number of new or enlarged gadolinium contrast-enhancing lesions measured on brain magnetic resonance imaging (MRI) scans every 4 weeks between weeks 8 and 24. Effects of daclizumab on prespecified subsets of immune system cells and immune system response were assessed in an exploratory substudy. The adjusted mean number of new or enlarged gadolinium contrast-enhancing lesions was 4.75 in the interferon beta/placebo group compared with 1.32 in the interferon beta plus high-dose daclizumab group and 3.58 in the interferon beta plus low-dose daclizumab group. In the substudy, daclizumab was not associated with significant changes in absolute numbers of T cells, B cells or T-cell proliferative response compared with interferon beta alone. The number of CD56bright natural killer cells was 7 to 8 times higher in both daclizumab groups than in the interferon beta/placebo group. Common adverse events were equally distributed across groups. "This study provides confirmatory data that daclizumab treatment causes an expansion of CD56bright natural killer cells and adds support to the theory that expansion of CD56bright natural killer cells might mediate some of the effects of daclizumab on reducing multiple sclerosis lesion activity," the authors wrote. "In addition to the results of previous trials of daclizumab in multiple sclerosis, several lines of evidence have suggested a potential immunoregulatory function for CD56bright natural killer cells: they are expanded during conditions of natural immune tolerance -- for example, pregnancy." "This randomised controlled trial indicates that daclizumab can reduce new lesion formation in relapsing multiple sclerosis compared with interferon beta alone...Multiple sclerosis treatments that have the potential to improve in risk-benefit ratios when compared with available treatments are needed; thus, additional studies to define the long-term clinical risks and benefits of daclizumab are warranted." In an accompanying comment, Olaf St�ve, MD, and Benjamin M. Greenberg, MD, Department of Neurology, University of Texas Southwestern Medical Center, Dallas, Texas, said: "All clinical and paraclinical evidence suggests that daclizumab mediates its beneficial effects at least partly through expanding regulatory CD56bright natural killer cells. It might now be time to explore further how these cells can be expanded in patients by other means... Identifying the physiological mechanism or mechanisms that lead to the expansion of these cells during disease remission might prove crucial in further understanding disease mechanisms and in developing novel therapeutics." Source: Doctors Guide Channels (c) 1995-2010 Doctor's Guide Publishing Limited. (16/02/10)

New diagnostic criteria for Multiple Sclerosis published

Mon, 15 Feb 2010 05:43:00 EST

Investigators are proposing new diagnostic standards for multiple sclerosis in clinically isolated syndromes. Their criteria are less stringent than other proposals and are designed to improve sensitivity to promote early diagnosis. The authors report they wanted to simplify existing diagnostic criteria for multiple sclerosis. The group, led by Xavier Montalban, MD, from the Hospital Universitari Vall d'Hebron, in Barcelona, Spain, suggests current recommendations are complex and that "a good working knowledge of them is not always evident even among neurologists and neuroradiologists." They point out that multiple magnetic resonance imaging (MRI) examinations are often needed to achieve an accurate diagnosis. "This provides an incentive for continued efforts to refine the incorporation of MRI-derived information into the diagnostic workup of patients presenting with a clinically isolated syndrome," they note. The new criteria appeared in the February 2 issue of Neurology. Recommendations �Clinically definite multiple sclerosis can be confirmed if a MRI is performed at any time demonstrating dissemination in space and showing at least 1 or more asymptomatic gadolinium-enhancing and nonenhancing lesions. �Patients without any enhancing or with all enhancing lesions would require a new MRI to demonstrate new T2 or gadolinium-enhancing lesions. �Patients with an abnormal MRI performed at any time, but not showing dissemination in space or time, would require follow-up imaging. "We recommend 1 dissemination in space criterion," the authors note. This would represent 1 or more asymptomatic T2 lesions in 2 or more of 4 locations considered characteristic for multiple sclerosis in previous MRI criteria � juxtacortical, periventricular, infratentorial, and spinal cord. "We recommend 2 dissemination in time criteria," they add, and call for the presence of at least 1 or more asymptomatic gadolinium-enhancing and nonenhancing lesions irrespective of the time of the scan and the presence of a new T2 or gadolinium-enhancing lesion compared with a previous scan. Asked by Medscape Neurology to comment on the new criteria, Gary Birnbaum, MD, from the Minneapolis Clinic of Neurology in Golden Valley, Minnesota, raised some concerns about the effect these recommendations could have. "The proposed criteria are less stringent than other criteria, possibly increasing the sensitivity of detecting conversion to clinically definite multiple sclerosis, but possibly decreasing the specificity of the changes," he said. "This will need to be monitored carefully." Increasing the Risk for Misdiagnosis Dr. Birnbaum says the data supporting early treatment of multiple sclerosis are good; however, he suggests that not all patients with clinically isolated syndrome need, or necessarily benefit from, treatment with disease-modifying therapies. "Indeed, recent long-term data show that more than 30% of persons with 'high-risk' MRI changes do not have significant disease after 20 years of follow-up," he said. "There may not be a great urgency for establishing a diagnosis of clinically definite multiple sclerosis in a significant proportion of individuals with clinically isolated syndrome, especially if the specificity of criteria are less stringent � increasing the risk of misdiagnosis." Dr. Birnbaum points out there are many disease-modifying therapies already approved for the treatment of patients with clinically isolated syndrome. "If a physician feels there is a need to begin treatment early, conversion to clinically definite multiple sclerosis is not necessary to prescribe such agents," he said. More Study Needed Dr. Birnbaum emphasizes that having less stringent MRI criteria for establishing disease progression may not be necessary and could increase the risk of treating people with diseases other than multiple sclerosis. Ben Thrower, MD, a neurologist and senior medical advisor for the Multiple Sclerosis Foundation, said he agrees there are risks involved in early diagnosis. This could lead to inaccurate diagnosis or patients starting therapy with expensive and inconvenient medications, he suggests. However, Dr. Thrower also acknowledges the benefits of early diagnosis, including peace of mind for patients and families dealing with unexplained symptoms. He points to data suggesting fewer relapses and new MRI lesions in those who start therapy sooner. "These new proposed guidelines offer the possibility of using a single MRI to fulfil diagnostic criteria," Dr. Thrower said. "If the brain MRI shows lesions with and without active inflammation, this would demonstrate dissemination in time and space." Dr. Thrower says the new criteria will need to be studied further and compared with existing McDonald criteria to determine whether they are sufficient. Dr. Montalban and his team acknowledge that testing these criteria in new, prospectively followed clinically isolated syndrome cohorts is needed. They also point out that scans in most studies have been performed on 1.5-Tesla or lower field-strength scanners using conventional T2-weighted spin echo or fluid-attenuated inversion recovery sequences. They note, "The impact of 3 Tesla or higher field MRI findings or other MRI sequences on diagnosis will have to be considered in the future." Dr. Xavier Montalban has received support from Novartis, Teva, Merck, Biogen Idec, Bayer, Schering Pharma, Sanofi-Aventis, Almirall, Eli Lilly, Genentech, Genzyme, Wyeth, and Fundaci� Esclerosi Multiple. Source: Medscape Today � 1994-2010 by WebMD LLC (15/02/10)

Preliminary results of preoperative diagnostics and endovascular treatment for CCSVI

Sat, 13 Feb 2010 05:03:00 EST

Preliminary results of preoperative diagnostics and endovascular treatment for CCSVI Marian Simka EuroMedicVascular and Endovascular Surgery Department Katowice Poland http://www.ms-mri.com/docs/Simka-hamilton%20-ccsvi-1.pdf

Blocking cell movement for possible Multiple Sclerosis treatment

Thu, 11 Feb 2010 07:06:00 EST

University of Adelaide researchers in Australia are finding new ways to block the movement of cells in the body which can cause autoimmune diseases and the spread of cancer. Led by Professor of Immunology Shaun McColl, the researchers have identified molecular "receptors" on the surface of cells which are involved in helping cells migrate to sites where they can cause disease. "A number of diseases like cancer and autoimmune diseases, such as multiple sclerosis and arthritis, involve the inappropriate migration of cells," says Professor McColl. "Our research shows that these receptors which help the cells migrate can be blocked pharmacologically, preventing the cell migration which causes the disease." The researchers have identified a number of such receptors in multiple sclerosis and have developed potential therapeutic drugs that could control this disease, and other autoimmune diseases. They are also in the process of identifying receptors on the surface of metastatic cancer cells. "These are exciting research outcomes and will offer new treatments for these diseases which affect millions of people," says Professor McColl. Professor McColl is Head of Chemokine Biology, Deputy Head of the School of Molecular and Biomedical Science and Deputy Executive Dean of the Faculty of Sciences at the University of Adelaide. Source: Science Daily � 1995-2009 ScienceDaily LLC (11/02/10)

Drinking milk during pregnancy lowers risk of multiple sclerosis in children

Wed, 10 Feb 2010 09:10:00 EST

Drinking milk during pregnancy reduces the chances of development of multiple sclerosis in children in their later life, says a new research study presented at the American Academy of Neurology�s annual meeting in Toronto, Canada. The researchers from the Harvard School of Public Health in Boston, US found that children born to pregnant mothers who drank milk were at lower risk of having multiple sclerosis. This was similar in cases where the mothers took vitamin D during pregnancy as well. Multiple sclerosis is a medical condition where the brain nerves are damaged and fails to communicate with the spinal cord. It may be seen relapsing in some cases and also show accumulation of the myelin sheaths over time. The common symptoms of this disease are weakness in muscles, spasms and difficulty in movement. A study of 35,794 female nurses whose their mothers provided information about their diet pattern during pregnancy established the link between multiple sclerosis and pregnancy. Out of those nurses who took part in the study, 199 were found to develop multiple sclerosis after a span of 16 years. The risk of multiple sclerosis was seen to be lower by 56 percent in daughters whose mothers drank milk (four glasses everyday) during pregnancy compared to those mothers who drank less than three glasses. The mothers who consumed vitamin D during pregnancy gave birth to daughters with 45 percent lower risk than those whose vitamin D intake was less. The findings of the study can help the mothers start having vitamin D and more milk during pregnancy to avoid their children suffer from multiple sclerosis when they grow up. Source: Bolo Health � 2009 Bolohealth.com (10/02/10)

Centre to test for Chronic Cerebrospinal Venous Insufficiency (CCSVI) and it's possible link to MS

Tue, 09 Feb 2010 02:41:00 EST

One of the first clinics in North America devoted to testing for a vascular condition that some experts believe is linked to multiple sclerosis is set to open later this month in Buffalo, just as scientists are to release more findings on the controversial theory. The Buffalo Neuroimaging Analysis Center (BNAC) has announced that it will begin to offer testing for the newly discovered condition, called chronic cerebrospinal venous insufficiency (CCSVI), in mid-February due to overwhelming demand from MS patients. Italian scientist Dr. Paolo Zamboni believes that CCSVI causes veins in the neck and upper chest to twist, narrow or become blocked; in some cases, these veins never form at all. The result is poor blood drainage from the brain. Zamboni has found that more than 90 per cent of patients with MS have these malformed veins, and improper blood flow from the brain. Due to the overwhelming response to Zamboni's research and to its own study on the condition, the BNAC said it will begin offering diagnostic venous testing to patients beginning in mid-February 2010. Testing will include: An MRI of the brain to measure the level of iron deposits An MRI of the neck to study the jugular, vertebral and other collateral veins A Doppler exam of the head and neck to determine blood flow A follow-up visit with a doctor to discuss the findings News of the findings comes days before scientists from the BNAC release data from their study that includes 500 MS patients who were tested for CCSVI. "What I can tell you today is that the preliminary results are exciting scientifically and will generate a great deal of discussion among our colleagues, the worldwide press, and individuals like you who are following very closely any developments about CCSVI," Dr. Robert Zivadinov said in the BNAC newsletter. Zivadinov said the second phase of the study will include another 500 patients and will "pose new and provocative questions about the CCSVI theory." Scientist welcomes scepticism Zamboni told CTV's Canada AM Monday that he welcomes skepticism about his findings. "This is normal when there is a new finding in science," Zamboni said. "I think that this is positive because it stimulates debate." Zamboni was in Hamilton, Ont., Sunday for a scientific workshop looking into the relationship between MS and CCSVI. Scientists from the United States, Europe and the Middle East reported that they had found CCSVI in more than 95 per cent of MS patients. "The meeting yesterday was quite successful because we met a lot of colleagues from all over the world that are actually working on our theory," said Zamboni, who is a professor of medicine at the University of Ferrara in Italy. According to Zamboni, a surgical procedure to restore proper blood flow, which he dubbed the "Liberation treatment," can reduce MS symptoms. In a study of 65 patients who underwent the procedure, released in the Journal of Vascular Surgery, Zamboni says that 50 per cent of patients with the most common form of MS were relapse-free for at least 18 months. In a control group of MS patients who did not undergo the procedure, only 27 per cent went 18 months without an MS attack. Additionally, only 12 per cent of patients in the surgery group had brain lesions -- a sign of active disease -- compared to 50 per cent in the control group. Research will take time Dr. Mark Haacke, director of the imaging division in the school of biomedical engineering at McMaster University, organized the weekend conference and said "no one is claiming it's a cure." "It's a cardiovascular problem first, it may be related to MS, it may cause MS -- but we don't know all those answers yet," he told CTV.ca. "That's going to take time to do very careful research to evaluate those MS patients that do get the operation. "Do they get better? Do they stay the same? Do their lesions go away? Or do they at least not get worse. (It) may take years and years to really determine the effectiveness of this surgery." MS societies around the world have responded with funding for research into CCSVI. The Italian Multiple Sclerosis Foundation has allocated up to $4.5 million for research and the MS Society of Canada has called for applications for grants for those studying Zamboni's findings. Charity Intelligence Canada, a group that provides donors with research and information, called for additional research and funding into Zamboni's findings on Monday. The group said Canadians donated $62 million to MS-related charities in 2009, and said "supporting CCSVI research presents an opportunity for donors to have high impact in their giving." "Donors wanting to support CCSVI research in Canada should donate directly to St. Joseph's Healthcare and McMaster University in Hamilton, Ontario and University of British Columbia, designating their donations to CCSVI research," the group said in a statement. However, experts have warned that the findings are far from being validated and those with MS should continue with their current treatment. "Although the early data are of great interest, it is important to acknowledge that the concept of CCSVI as a cause of MS and the use of stents or balloons to widen veins as treatments, are ideas that are far from being accepted by most researchers in the field," the MS Society of Canada says on its website. Experts have expressed concern that the initial excitement over the new procedure was leading some to drop their current treatment. "To people with MS we say: don't abandon the course of treatment that you have started," Yves Savoie, the president and CEO of the MS Society of Canada told CTV News in November. "Those treatments have been proven in large trials to be effective in reducing the burden of disability that comes with MS." Haacke says that since most MS patients have MR scans performed, clinicians should consider performing additional scans for CCSVI. "It's important for clinicians to begin to realize that they should be taking some time clinically � not on the research side � to scan their patients and find out if this is a problem," he said. Canada has one of the highest rates of MS in the world, affecting between 44,000 to 78,000 in the country. Source: CTV News � 2010 CTVGlobeMedia (09/02/10)

New theory suggests Multiple Sclerosis treatable

Mon, 08 Feb 2010 09:34:00 EST

A controversial theory touting multiple sclerosis as a vascular disease is a "step in the right direction" but not a panacea, says a McMaster University professor. Dr. Mark Haacke, director of the imaging division in the school of biomedical engineering at Mac, says it would not be a good idea for people to call the theory by Dr. Paolo Zamboni a cure for the disease. "I think the key here is that these people who've had the disease, it may take a long time for the problems in the brain to clear up," said Haacke, who is also a professor at Wayne State University. "They may still require the conventional treatments that they're getting now." Zamboni has proposed that multiple sclerosis (MS) is a vascular disease that can be treated, rather than an auto-immune disorder with few treatment options. His theory is called chronic cerebrospinal venous insufficiency. He was in Hamilton yesterday for a scientific workshop at St. Joseph's Healthcare's Charlton Avenue site. About 200 people, a mix of professionals, doctors, scientists, and people who suffer from MS attended. The workshop was a closed event. "I think it went very well," said Kevin Smith, CEO of St. Joseph's Healthcare. "Obviously this was an opportunity for the scientific community to come together and chat with Professor Zamboni about his observations and others who've been involved in replicating his observations." In addition to Zamboni, those in attendance say information from others doing similar work around the globe was presented. Dr. Ian Rodger, vice-president of research at St. Joe's, said the workshop heard "undeniably" that there are patients who have had the medical procedure that is done based on his theory (it unclogs veins to the brain and improves blood flow) who quickly had relief from some MS symptoms such as fatigue and buzzing in their ears. "What we don't know is how long does it last? ... No one's been following it long enough. But I think at the end of it all, (it's) highly encouraging that the data is steadily coming out." Rodger also said Zamboni has not presented something "mind-shattering" as talk about problems with blood vessels in the brain leading to MS was around 100 years ago. Smith said the MS Society of Canada has now put out a call for proposals to research the subject further. St. Joe's and McMaster will be involved in bidding for the chance to conduct the study, he said. St. Joe's has currently done some imaging work around the theory and was swamped with 22,000 request from MS patients wanting to take part. Source: Thespec.com � Copyright Metroland 2010 (08/02/10)

African/Americans with MS have more severe symptoms, decline faster than whites

Mon, 08 Feb 2010 05:43:00 EST

Fewer African Americans than Caucasians develop multiple sclerosis (MS), statistics show, but their disease progresses more rapidly, and they don't respond as well to therapies, a new study by neurology researchers at the University at Buffalo has found. Magnetic resonance images (MRI) of a cohort of 567 consecutive MS patients showed that blacks with MS had more damage to brain tissue and had less normal white and grey matter compared to whites with the disease. Results of the study appear in the Feb. 16 issue of the journal Neurology. Bianca Weinstock-Guttman, MD, UB associate professor of neurology in the UB School of Medicine and Biomedical Sciences, is first author on the study. Weinstock-Guttman directs the Baird Multiple Sclerosis Center in Kaleida Health's Buffalo General Hospital. "Black patients showed more brain tissue damage and accumulated brain lesions faster than whites, along with rapid clinical deterioration," confirms Weinstock-Guttman. "The results provide further support that black patients experience a more severe disease, calling for individualised therapeutic interventions for this group of MS patients." "White matter" refers to the parts of the brain that contain nerve fibers sheathed in a white fatty insulating protein called myelin. The white matter is responsible for communication between the various grey matter regions, where nerve cells are concentrated and where cognitive processing occurs. "Initially, multiple sclerosis was considered primary a white-matter disease," says Weinstock-Guttman, "but today we know that the grey matter may be more affected than white matter." In general, black MS patients tend to have more severe and more frequent attacks, followed by an incomplete recovery even after the first episode. Studies on signs and symptoms of MS among populations have shown that blacks experience gait problems sooner after their diagnosis, show faster cognitive decline than whites with MS, and become dependent on a wheelchair sooner, she notes. The study's MRI scans were conducted at the Buffalo Neuroimaging Analysis Center (BNAC), part of the Jacobs Neurological Institute/UB Department of Neurology. Robert Zivadinov, MD, PhD, a UB associate professor of neurology, is director of the center. Seventy-nine black patients and 488 white patients were entered in the study. Participants were older than 18 and had been scanned within 90 days of their most recent clinical visit. Black participants were significantly younger, and their disease was more severe than white patients, despite having MS for a shorter amount of time. "Results of the MRI scans showed that the aggressive disease process in blacks appears to be associated with increased macroscopic and microscopic tissue damage, as measured by specific MRI parameters," says Weinstock-Guttman. "Based on our MRI findings, a plausible hypothesis that would explain the more aggressive disease in blacks compared to whites with MS may be that blacks have a reduced capacity for remyelination, the brain's ability to repair the protective myelin sheath. However, to confirm this hypothesis, we will need to conduct more longitudinal studies." Murali Ramanathan, PhD, associate professor in the departments of Pharmaceutical Sciences and Neurology in the UB School of Pharmacy and Pharmaceutical Sciences and School of Medicine and Biomedical Sciences, respectively, also contributed significantly to the study. Additional contributors were David Hojnacki, MD, Michael G. Dwyer, Sara M. Hussein, MD, Niels P. Bergsland and Frederick E. Munschauer, MD, former chair of the UB Neurology department, now vice president of U.S. medical affairs for Biogen Idec in Boston, Mass. The study was supported by grants from the National Multiple Sclerosis Society and the UB Pediatric MS Center of Excellence. The University at Buffalo is a premier research-intensive public university, a flagship institution in the State University of New York system and its largest and most comprehensive campus. UB's more than 28,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs. Founded in 1846, the University at Buffalo is a member of the Association of American Universities. Source: University of Buffalo � 2010 University at Buffalo.(08/02/10)

Test of CCSVI - Multiple Sclerosis theory 'watershed moment' for St. Joe's

Sun, 07 Feb 2010 03:06:00 EST

Finding a treatment for multiple sclerosis holds as much promise for Hamilton as it does for patients. St. Joseph's Hospital is one of just two places in Canada testing Italian vascular surgeon Dr. Paolo Zamboni's controversial theory that MS is a vascular disease -- a radical departure from long-held beliefs that it's an autoimmune condition. The University of British Columbia is the other place. It has brought Hamilton to the attention of the world with about 22,000 MS patients from Asia to Africa to South America to all over the United States and Canada vying to be one of the 100 chosen for the study. It will also recruit 100 healthy people to take part. "This is a watershed moment," said Dr. Ian Rodger, vice-president of research at St. Joseph's Healthcare. "Opportunities like this don't come along very often." Hamilton has the chance because of McMaster's affiliation with Detroit imaging expert Dr. Mark Haacke, who met Zamboni in September when the Italian doctor held a conference about his theory. Zamboni believes the veins draining blood from the brain are blocked and leaking in MS patients. This allows iron to leak into brain tissue and he thinks the buildup causes many symptoms of MS. Zamboni found those veins blocked or malformed in more than 90 per cent of MS patients he studied -- including his wife. Haacke has long researched the role iron plays in MS and is eager to test Zamboni's theory. His main lab is in Detroit but he's also an adjunct professor at McMaster. With eight other Hamilton doctors, he plans to use St. Joseph's MRI, which is twice as strong as traditional machines, to look at the veins in the brains of MS patients and healthy people to see whether there is a difference. Haacke says there has been a lot of resistance to Zamboni's theory -- Chronic Cerebrospinal Venous Insufficiency (CCSVI) -- from medical professionals, particularly neurologists. "It was just so flabbergasting to them," he said. But the idea can't be ignored. "We're going to have 10 years of fascinating research." St. Joseph's, McMaster and Hamilton Health Sciences want to play a big role in that. They don't have funding yet, but are together putting in a proposal to the MS Society of Canada Tuesday for $100,000 a year for two years. Rodger is leading the research and hoping other funders will come forward so that they can do a much bigger study that would produce results in 12 to 15 months instead of two years or longer. Philanthropists and/or their advisors are expected to be at the workshop Zamboni and Haacke are presenting in Hamilton tomorrow. The stakes are high for MS patients, as there are few treatment options. Zamboni performs an experimental surgery similar to angioplasty to unclog the veins and improve blood flow. He says it has worked for his wife and others. Hamilton MS patient Vasilios "Bill" Smyrnios wants to know if that surgery could help him. The 50-year-old who was diagnosed 10 years ago can't walk anymore and has to live in supportive housing. "This disease is relentless," he said. "It keeps getting worse. It has amazed me. I never expected to get like this." He has newfound hope since researching Zamboni's theory. "It was the first thing I've read in a long time that made sense." While St. Joseph's is studying the theory and hosting the conference, it is a long way from endorsing it. "There's a great deal of skepticism about the observational study (that Zamboni did)," said Kevin Smith, CEO of St. Joseph's Healthcare. "A lot of the scientific community has already rejected the view. But it resonates profoundly with patients and families so it's our responsibility to determine if this is more than unusual observation." Source: Thespec.com � Copyright Metroland 2010 (07/02/10)

New study planned to test earlier use of Multiple Sclerosis drug Tysabri

Sun, 07 Feb 2010 02:01:00 EST

Biogen Idec Inc. is planning the first clinical trial that could lead to use of controversial multiple sclerosis treatment Tysabri, sold with Elan Corp, at earlier stages of the disease. The long-term trial, dubbed Surpass, will measure the effectiveness of Tysabri in patients with active MS that have switched from either Teva Pharmaceutical Industries Ltd.'s Copaxone or Rebif, sold by Pfizer Inc. and Germany's Merck KGaA. Tysabri is considered a highly effective therapy for MS, and its growth is important to the future of both Elan and Biogen. But its sales have been slower than originally hoped amid concerns about the risk of a rare brain infection that led to its 18-month market withdrawal beginning in 2005. The study comes after Tysabri brought in more than $1 billion in 2009, and it is part of Biogen's push to accelerate Tysabri's growth. It also comes amid increased competition in MS treatments. Novartis AG and Germany's Merck KGaA could launch oral treatments for the disease this year, a notable advance compared to the injections and infusions required with current drugs. The goal of the Surpass trial is to get physicians to use Tysabri when patients aren't responding to their current therapy, rather than switching them to more mainstream therapies. Beside Copaxone and Rebif, other common options include Biogen's Avonex and Bayer AG's Betaseron, while Tysabri is generally reserved for patients with very aggressive disease or have no other options. "We are trying to establish that there is no use in switching around [prior to using Tysabri]," Biogen spokeswoman Naomi Aoki. The company is signing up sites for the trial and has yet to enroll the first of an estimated 1,800 patients. The study will follow participants for about two years and isn't likely to yield data until 2013 or 2014. If successful, the result should allow Biogen to update Tysabri's label and allow it to market the earlier use to physicians. Source: ADVFN III Copyright 1999-2010 ADVFN PLC (07/02/10)

New FDA warning on Multiple Sclerosis drug, Tysabri, greater number of doses raises risk of brain infection

Sat, 06 Feb 2010 02:21:00 EST

In the latest blow to the controversial multiple sclerosis drug Tysabri, the U.S. Food and Drug Administration announced that it was slapping a new warning on the drug's label. In an advisory sent to health-care professionals and patients, the FDA warned that the risk of developing progressive multifocal leukoencephalopathy (PML), a rare but deadly brain infection, increases as more infusions are received. "This is updated information, taking new cases into account," explained Dr. William Sheremata, professor emeritus of neurology at the University of Miami Miller School of Medicine, who gave the drug to the first humans. European patients account for most of the new cases and many of them might have been taking multiple drugs, raising their risk for PML, he added. "This is not new information. We've had this information for a couple of months now [but] the labeling in the past did not make a distinction between the time frames that people were on the drugs," said Dr. John Richert, executive vice president for research and clinical programs at the National Multiple Sclerosis Society. "The risk-benefit ratio continues to be about the same as we anticipated since the time the drug was brought back on the market." Another expert agreed that the clinical picture hasn't been altered by the new label warning. "I think as long as the medication is being prescribed for the appropriate patient with MS, then the new information we have today is not going to alter medication management," said Dr. Jeffrey Tramonte, director of neurology at the Scott & White University Medical Campus in Round Rock, Texas. "Right now, Tysabri is the most efficacious drug that's ever been approved for the treatment of relapsing-remitting MS, which represents 85 percent of all patients out there who have MS," he said. "However, it also carries the single most dangerous risk factor, and that's PML," added Tramonte, who only gives Tysabri if his patients have failed or have severe side effects from conventional immunomodulating drugs. Natalizumab (Tysabri) first received FDA approval in November 2004, only to be pulled from the market three months later after several patients in clinical trials developed PML. In June 2006, the FDA allowed the drug back on the market, but with strict conditions. According to those revised guidelines, Tysabri can only be administered by approved doctors, at infusion sites and at pharmacies that register and comply with a patient-safety program called CD Touch, designed by drugmaker Biogen Idec and approved by the FDA. The FDA said the new action was based on reports of 31 confirmed cases of PML as of Jan. 21, 2010. Information on the risk will also be included in the patient Medication Guide. However, the FDA did not suggest discontinuing the drug, stating that it "believes that the clinical benefits of Tysabri continue to outweigh the potential risks." The drug was approved to treat Crohn's disease in early 2008. It is also linked with liver damage. Patients do take the drug long-term, Richert said. Source: HealthDay � 2010 HealthDay. (06/02/10)

Compugen discovers CGEN-15001 protein for treatment of autoimmune disorders

Wed, 03 Feb 2010 05:14:00 EST

Compugen Ltd. announced today the discovery and experimental validation of CGEN-15001 for the treatment of autoimmune disorders. CGEN-15001 is the extracellular region of a previously unknown membrane protein in the B7/CD28 family. The existence and potential utility of the newly discovered parent protein from which CGEN-15001 is derived was predicted in silico utilizing Compugen�s LEADS Platform and other proprietary algorithms. Autoimmune diseases develop when defects in the immune system lead the body to attack its own cells, tissues, and organs and include more than 80 chronic, and often disabling, illnesses. Among the most common autoimmune diseases are rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease, and type 1 diabetes. Collectively, autoimmune diseases are among the most prevalent diseases, affecting an estimated 25 million people in the U.S. CGEN-15001 is a novel soluble recombinant fusion protein corresponding to the extracellular region of the Compugen discovered parent protein. The discovery of the parent protein, which is a membrane protein, was accomplished through the incorporation in Compugen�s LEADS Platform of additional algorithms specifically designed to predict novel members of the B7/CD28 family of co-stimulatory proteins. This approach relied on Compugen�s proprietary understandings and modeling of genomic structure, gene expression, protein structural domains, and cellular localization. Compugen has filed for patent coverage on both the parent protein, which potentially has other medical uses such as a target for antibody therapeutics, and CGEN-15001. The in vivo validation of CGEN-15001 utilized a mouse model of multiple sclerosis, relapsing-remitting experimental autoimmune encephalomyelitis (R-EAE). In this model, administration of CGEN-15001 resulted in potent amelioration of the disease state. These results indicate that CGEN-15001 could have therapeutic utility for the treatment of multiple sclerosis and other autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, and type 1 diabetes. Earlier in vitro studies validated the predicted functional activity of CGEN-15001 as a new member of the B7/CD28 family proteins. Professor Stephen Miller from Northwestern University, a leading scientist in this field who supervised the studies, stated, �Our studies have indicated robust disease suppressing activity for CGEN-15001 in the SJL R-EAE model, a recognized mouse model for multiple sclerosis. These studies have also demonstrated that CGEN-15001 has the unique ability to inhibit proliferation, differentiation, and cytokine production of pro-inflammatory Th1 and Th17 responses while at the same time sparing or actually promoting regulatory Th2-derived cytokines. As far as I am aware, this potentially very beneficial pattern of inhibiting Th1/Th17 while promoting Th2 responses is unique among the reagents targeting the B7 family of co-stimulatory molecules that have been published to date.� Compugen�s VP R&D, Dr. Zurit Levine stated, �We are extremely pleased by this further demonstration of the unique discovery capability that has been created at Compugen. In view of its recognized potential in the largely unmet and critical field of immune regulation, the B7/CD28 co-stimulation protein family has been an area of extensive research for a number of years. In our opinion, in addition to providing Compugen with a very attractive product candidate, the predictive discovery and experimental validation of a previously unknown member of this extensively researched protein family represents a major milestone in the transition from experimentally based therapeutic discovery to in silico prediction and selection.� Source: Compugen Ltd. (03/02/10)

The rising prevalence and changing age distribution of multiple sclerosis in Manitoba

Wed, 03 Feb 2010 03:59:00 EST

Summary Several studies suggest an increasing prevalence of multiple sclerosis (MS) in Canada. Canadian MS neurologist and researcher Dr. Marrie and colleagues aimed to validate a case definition for MS using administrative health insurance data, and to describe the incidence and prevalence of MS in Manitoba, Canada. Neurology. 2010 Jan 13. [Epub ahead of print] Details Provincial administrative claims data were reviewed to identify persons with demyelinating disease using International Classification of Diseases 9/10 codes and prescription claims. Questionnaires were mailed to 2,000 randomly selected persons with an encounter for demyelinating disease, requesting permission for medical records review. Diagnoses abstracted from medical records were used as the gold standard to evaluate candidate case definitions using administrative data. From 1984 to 1997, cases of MS using claims data were defined as persons with seven or more medical contacts for MS. From 1998 onward, cases were defined as persons with three or more medical contacts. As compared to medical records, this definition had a positive predictive value of 80.5% and negative predictive value of 75.5%. From 1998 to 2006, the average age- and sex-adjusted annual incidence of MS per 100,000 population was 11.4 (95% confidence interval [CI] 10.7-12.0). The age-adjusted prevalence of MS per 100,000 population increased from 32.6 (95% CI 29.4-35.8) in 1984 to 226.7 (95% CI 218.1-235.3) in 2006, with the peak prevalence shifting to older age groups. Authors conclude that the prevalence of multiple sclerosis (MS) in Manitoba is among the highest in the world. The rising prevalence with minimally changing incidence suggests improving survival. This study supports the use of administrative data to develop case definitions and further define the epidemiology of MS. Source: MS Society of Canada National Research and Programs (03/02/10)

Pregnancy changes the expression of inflammation-related genes in patients with Multiple Sclerosis

Wed, 03 Feb 2010 03:59:00 EST

Pregnancy is associated with reduced activity of multiple sclerosis (MS). However, the biological mechanisms underlying this pregnancy-related decrease in disease activity are poorly understood. We conducted a genome-wide transcription analysis in peripheral blood mononuclear cells (PBMCs) from 12 women (7 MS patients and 5 healthy controls) followed during their pregnancy. Samples were obtained before, during (i.e. at the third, sixth, and ninth month of gestation) and after pregnancy. A validation of the expression profiles has been conducted by using the same samples and an independent group of 25 MS patients and 11 healthy controls. Finally, considering the total group of 32 MS patients, we compared expression profiles of patients relapsing during pregnancy (n = 6) with those of relapse-free patients (n = 26). Results showed an altered expression of 347 transcripts in non-pregnant MS patients with respect to non-pregnant healthy controls. Complementary changes in expression, occurring during pregnancy, reverted the previous imbalance particularly for seven inflammation-related transcripts, i.e. SOCS2, TNFAIP3, NR4A2, CXCR4, POLR2J, FAM49B, and STAG3L1. Longitudinal analysis showed that the overall deregulation of gene expression reverted to �normal� already within the third month of gestation, while in the post-partum gene expressions rebounded to pre-pregnancy levels. Six (18.7%) of the 32 MS patients had a relapse during pregnancy, mostly in the first trimester. The latter showed delayed expression profiles when compared to relapse-free patients: in these patients expression imbalance was reverted later in the pregnancy, i.e. at sixth month. Specific changes in expression during pregnancy were associated with a decrease in disease activity assessed by occurrence of relapses during pregnancy. Findings might help in understanding the pathogenesis of MS and may provide basis for the development of novel therapeutic strategies. Francesca Gilli1*, Raija L. P. Lindberg2, Paola Valentino1, Fabiana Marnetto1, Simona Malucchi1, Arianna Sala1, Marco Capobianco1, Alessia di Sapio1, Francesca Sperli1, Ludwig Kappos2, Raffaele A. Calogero3, Antonio Bertolotto1 1 Regional Centre for Multiple Sclerosis (CReSM) and Clinical Neurobiology, Azienda Ospedaliera Universitaria San Luigi Gonzaga, Orbassano, Italy, 2 Departments of Biomedicine and Neurology, University Hospital Basel, Basel, Switzerland, 3 Genomics and Bioinformatics Unit, Department of Clinical and Biological Sciences, Azienda Ospedaliera Universitaria San Luigi Gonzaga, Orbassano, Italy Full Paper - http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0008962 Source: PLoS ONE � 2010 Gilli et al. (02/02/10)

Australian study questions established concepts of early disease events in MS

Sat, 30 Jan 2010 03:04:00 EST

Investigators at the University of Sydney have published a study suggesting that the earliest activity seen in the brain in MS is the destruction of cells that make myelin (oligodendrocytes), occurring before the onset of immune activity usually blamed for triggering the disease. This provocative study, co-funded by many sources including the National MS Society, opens up new possibilities for finding the cause of the disease and developing new treatments. The study is authored by Drs. John W. Prineas, Andrew P.D. Henderson and colleagues, and is published in the December issue of Annals of Neurology (2009;66:739�753). Background: Multiple sclerosis has long been thought to be triggered by immune attacks in the brain and spinal cord, causing a spectrum of neurological symptoms. Extensive research has been underway to better understand what triggers the immune attacks and which immune cells are involved, and to better understand the damage to the central nervous system that occurs during the course of MS. In addition to studies of immune activity underlying what has been considered an autoimmune process, another important approach has centered on pathology studies involving microscopic explorations of MS lesions (damaged areas, also called plaques) in the brains of people with MS. The lead author of the current study, John W. Prineas, MB, BS, FRCP, was the 2001 winner of the John Dystel Prize for MS Research, an award given jointly by the National MS Society and the American Academy of Neurology. He was recognized for being the investigator who first described how myelin, the substance that insulates nerve fibers, is broken down in MS, and he was the first to demonstrate that myelin repair occurs during the course of MS through the body�s natural repair processes. Current Study: For this study, the team used brain specimens from 11 people who had died early in the course of their MS, and the team also used comparison specimens from people with other disorders including stroke. Some of the tests focused on subsets of specimens from seven people who had lesions showing active myelin destruction. To get a sense of immune cell activity in the brain and at what stage it was occurring, the team examined newly active and resolved lesions, as well as nearby blood vessels, surrounding areas showing some disease activity and surrounding areas that appeared normal, and areas that were farther away from the lesions of interest. Results: In tissues surrounding newly forming lesions, the investigators found evidence of the loss of oligodendrocytes with an absence of immune T or B cells that would normally be held responsible for launching the immune attack against oligodendrocytes and the myelin they produce. These and other immune cells, including scavenger cells (macrophages and microglia), were more numerous in lesions and surrounding tissues at apparently later stages of destruction and sometimes in lesions that were in the process of repair. In specimens from two very early cases of clinical onset of disease, they found few immune cells within the lesions and no evidence of activation of scavenger cells. These and other unexpected findings from this study led the investigators to propose that the early immune activity seen in active lesions is that of macrophages and microglia, whose job it is to clean up and remove damaged myelin. They propose that lesion formation is caused by something other than destructive immune activity led by inflammatory cells against a component of myelin or oligodendrocytes. Comment: This study is a significant addition to a small but growing body of evidence that highlights the question of what triggers MS and whether there is something other than, or in addition to, the immune attacks that lead to tissue damage in the brain and spinal cord of people with MS. Further research, which is ongoing by investigators around the world, should shed further light on this question and may offer novel treatment approaches. Note: The availability of donor brain specimens was crucial to this and other studies focusing on disease pathology Source: US National Multiple Sclerosis Society (30/01/10)

Could stem cells reverse Multiple Sclerosis?

Fri, 29 Jan 2010 03:02:00 EST

Biologist Tom Lane and a team of UCI researchers are leading an effort to determine whether a stem-cell-based treatment can repair neurological damage caused by multiple sclerosis. More than eight years ago, Tom Lane helped discover a potential way to prevent multiple sclerosis from affecting the central nervous system. Now he�s leading an effort at UC Irvine to determine whether a stem-cell-based treatment can repair neurological damage caused by the chronic disease. Lane, a molecular biology & biochemistry professor, is among 15 U.S. researchers who recently received five-year Collaborative MS Research Center Awards from the National Multiple Sclerosis Society. With the $742,500 in funding, he has assembled a team to investigate the use of cell-replacement therapy to regenerate MS-ravaged nerve tissue. In people with MS, immune-system T cells attack myelin, the protective coating of nerves, and eventually the nerve fibers themselves. Symptoms may be mild, such as intermittent numbness in the limbs, or severe, such as paralysis or loss of vision. There is no cure for MS, and current treatments mainly try to limit immune-system response. �The promise of cell-replacement strategies to treat MS is significant,� Lane says. �Imagine being able to infuse people with cells that could make new myelin or transform into healthy nerve cells. That�s the focus of our effort.� Spinal cord injury research at UCI has already shown the potential of cell-replacement therapy to repair myelin. Neurobiologist Hans Keirstead pioneered a technique to turn human embryonic stem cells into myelin-making oligodendrocyte precursor cells (OPCs) that, he demonstrated, can restore impaired nerve function. These findings form the basis of an upcoming clinical trial involving people with acute spinal cord injury. With Keirstead providing the cell lines, the UCI team will explore OPCs� ability to repair MS-related myelin damage and how the cells could be safely introduced into the body. Researchers and their topics include: � Lane studying immune-system messenger cells called chemokines that permit the migration of OPCs to their targeted nerve sites. � Dr. George Chandy, physiology & biophysics professor, investigating methods of muting T cell response while OPCs reconstruct myelin. � Michael Cahalan, physiology & biophysics professor and chair, developing ways to track and visualize the migration of stem cells and immune cells within the living central nervous system. � Dr. Michael Demetriou, associate professor of neurology and director of the comprehensive MS program at UC Irvine Medical Center, examining how enzymes direct T cells and, possibly, OPCs. � Dr. Steven Schreiber, neurology professor and interim chair, determining whether niacin can increase the repair capacity of OPCs. �With the knowledge acquired from these studies, we believe we�ll lay the foundation for the creation of safe and effective treatments to improve quality of life for people with MS,� Lane says. �UCI has long been a leader in MS research and patient care, and it�s exciting to be part of the significant impact our researchers and clinicians make in this field.� Source: Physorg.com � PhysOrg.com 2003-2009 (29/01/10)

MRI study evaluates dynamic causal model to assess interactions of brain regions during motor task in Multiple Sclerosis patients

Fri, 29 Jan 2010 02:25:00 EST

The use of functional MRI to assess patterns of brain activation in adults and children with multiple sclerosis (MS) may offer insight into disease progression among these groups, according to research published in the February issue of Radiology. Maria A. Rocca, M.D., of the University Hospital San Raffaele in Milan, Italy, and colleagues analyzed data from five small groups: healthy pediatric and adult controls, pediatric and adult patients with relapsing-remitting MS, and adults with clinically isolated syndromes. Patients underwent MRI during a simple motor task. Also, a dynamic causal model approach was used to assess interactions between different regions during the task. The researcher's findings suggest that the brain pattern of cortical activation is relatively preserved in pediatric relapsing-remitting patients, and additional areas of the network are progressively recruited in adult relapsing-remitting patients. The relatively preserved adaptive properties of the cerebral cortex in pediatric patients may inhibit clinical disability in the short to medium term. "The preservation of brain adaptive properties might explain the favorable medium-term clinical outcome of pediatric MS patients," the authors write. "The progressive recruitment of cortical networks over time in patients with the adult relapsing-remitting forms of the disease might result in a loss of their plastic reservoir, thus possibly contributing to subsequent disease evolution." Abstract Source: Modern Medicine � 2010 HealthDay. (29/01/10)

Skin cells turned directly into neurons

Fri, 29 Jan 2010 01:31:00 EST

Stem cell scientists at Stanford University in California announced "a huge step forward", with the publication of research that turned skin into nerve cells without any intermediate step. The production of neurons [nerve cells] directly from other adult cells, without making stem cells en route, could transform "regenerative medicine" - providing a plentiful supply of neurons for treating people with degenerative brain diseases such as Parkinson's or those with spinal injuries. "We actively and directly induced one cell type to become a completely different cell type," said Marius Wernig of Stanford's Institute for Stem Cell Biology and Regenerative Medicine. "These are fully functional neurons. They can do all the principal things that neurons in the brain do." This includes making connections with and signalling to other nerve cells - critical functions if the cells are eventually to be used as therapy for brain disease. The study is published online in the journal Nature . Although research had suggested that specialised cells could be coaxed to show properties of other cell types, this is the first time skin cells have been converted into neurons in a laboratory. The change happened within a week of treating mouse skin cells with a mixture of three genes, with an efficiency of up to nearly 20 per cent. The scientists are now working to duplicate the feat with human cells. Until recently, scientists believed cellular differentiation was a one-way process, with primitive and versatile embryonic stem cells giving rise to all the body's more specialised cells. Then, in 2007 they discovered how to turn the clock back, reversing the specialisation process by converting adult cells to "induced pluripotent stem cells", which could then become a different type of cell. The latest discovery shows that this intermediate step is unnecessary. But many years of work will be needed before direct conversion reaches the clinic. Source: The Financial Times Copyright The Financial Times Limited 2010. (29/01/10)

Biogen starts human trial of drug that could repair Multiple Sclerosis damage

Wed, 27 Jan 2010 11:38:00 EST

Biogen Idec Inc. has begin human testing of an experimental drug, dubbed BIIB033, that it hopes will take the revolutionary step of repairing some of the damage done by multiple sclerosis. Although it is a major step to begin testing in humans, drug development is always risky and it will take years to measure the drug's effectiveness and potential side effects. Multiple sclerosis, or MS, is a chronic, inflammatory condition that occurs when the body attacks its own myelin, the protective insulation surrounding the nerve fibers, or axons, in the central nervous system. The debilitating disease affects an estimated 400,000 people in the U.S., according to the National MS Society, but current treatments only aim to slow the disease's progression and cannot help repair damage. Research that focuses on ways to help the body regenerate myelin is growing and scientists around the world are taking several different approaches. Damage to myelin can distort or block messages carried by axons and result in a wide variety of MS symptoms such as vision problems, limb numbness and paralysis. BIIB033 is an antibody designed to turn off Lingo-1, a molecule that the company believes prevents myelin production in adults after axons are well covered. Blocking Lingo-1 may encourage myelin regeneration, something that occurs in healthy adults, after damage from MS occurs. The antibody has been shown to be effective in mouse models that are accepted as being useful for mimicking the properties of MS. The small Phase I study will include 64 healthy volunteer adults in the Netherlands, with the main goal of assessing safety and tolerability, and is expected to be completed in 2011. The placebo-contolled study will give patients a single dose of the drug and different groups will get different amounts, a standard practice in such early trials that helps determine the optimal dose for later investigation. The secondary goals of the trial relate to how the body processes the drug and there is no measure of its effectiveness, which is not surprising in such an early study that doesn't actually include MS patients. MS is an attractive area of drug makers as its often requires lifelong treatment, and MS drugs brought in more than $8.7 billion in 2009 revenue worldwide, according to projections from Bernstein Research. Biogen is mostly focused on selling MS treatments, including Tysabri and Avonex, which are expected to bring sales of more than $3 billion for 2009. Source: Dow Jones Newswires (c) 2010 Dow Jones & Company, Inc. (27/01/10)

More checks for Multiple Sclerosis drug Tysabri

Wed, 27 Jan 2010 02:34:00 EST

Last week, the European Medicines Agency (EMEA) finalized a review of Biogen Idec�s Tysabri (natalizumab) and the risk of progressive multifocal leukoencephalopathy (PML) associated with the prolonged use of the drug. PML is a rare brain infection caused by the JC virus. The agency�s Committee for Medicinal Products for Human Use (CHMP) arrived at the conclusion that the risk of a patient developing PML increases after having taken the drug for two years or more, though the risk remains low. However, the benefits of the drug outweigh its risks. Given the importance of the early detection of PML, the committee has recommended certain measures to ensure that patients and doctors are aware of the associated risks. Measures include updating product information to include the high risk of developing PML after two years of treatment and advice regarding management of patients showing symptoms of PML. In addition, the committee suggested that forms should be signed by patients at the beginning and after two years of treatment after having discussed the risks with their doctors. The CHMP had to review the drug after 23 confirmed cases of PML were reported between July 2008 and October 2009, causing four deaths. Fourteen of these cases including one death were reported in the EU. Subsequently, the European Commission in October 2009 requested CHMP�s opinion for Tysabri. As of January 20, 2010, the total number of PML cases has risen to 31, of which 23 were patients who had been receiving the drug for more than two years. This is equivalent to approximately one case of PML for every 1,000 patients treated with Tysabri for two years or more, consistent with the risk mentioned in the Tysabri�s label. Tysabri, meant for the treatment of multiple sclerosis (MS) is jointly marketed with Elan Corp. The drug was withdrawn from the U.S. market in 2005 due to the PML concern, but was launched again after one year with a strict warning regarding the occurrence of PML. Source: Yahoo! Finance � 2010 Yahoo! (27/01/10)

Tysabri PML updates set to start again

Tue, 26 Jan 2010 03:42:00 EST

The maker of Tysabri will once again provide monthly updates regarding new cases of progressive multifocal leukoencephalopathy, or PML, an often fatal brain infection seen in some people treated with the multiple sclerosis (MS) drug. Biogen Idec Inc. had stopped providing the monthly PML updates last summer. Tysabri is seen as one of the most effective MS treatments on the market, especially for those with severe cases who have few other options. Unfortunately, it also poses serious risks because of its association with PML. PML attacks the brain and central nervous system and is usually fatal. It is caused by a polyomavirus, called the JC virus. The JC virus is often acquired during childhood. Most adults have been infected with the JC virus but do not develop PML. The virus appears to remain inactive until something (such as a weakened immune system) allows it to be reactivated and start to multiply. Symptoms include vision problems, loss of coordination, and memory loss. Patients who survive the disease are often permanently disabled. In the U.S. Tysabri was taken off the market in 2005 after three patients in clinical trials developed PML. But the drug was reapproved in 2006, although it was subject to restrictions. Tysabri is now available only to patients with relapsing MS or Crohn�s Disease who are enrolled in the risk minimization plan called the TOUCH Prescribing Program. Under the TOUCH Prescribing Program, every Tysabri-treated patient is closely monitored and followed for the occurrence of PML and other serious opportunistic infections. In September, the U.S. Food & Drug Administration (FDA) revealed that 24 cases of PML had been reported in Tysabri users, more than double the 11 Biogen Idec had disclosed at its final monthly update in July. As of mid-January, the number of PML cases among people treated with Tysabri stands at 31. According to The Wall Street Journal, through the new Tysabri monitoring program, Biogen Idec will update physicians about new PML cases at the middle of each month. Doctors will be able to access this information through a password-protected Web site. In addition to the number of PML cases, Biogen Idec will provide details on duration of use, as well as a cumulative patient exposure figure. Investors will be able to access the same information via Investor Relations. According to the Journal, no public Web site will be launched to provide the information. Tysabri patients can request the information, but the information they will be provided will not be as detailed as what doctors, or even investors, are give. The disparity is the result of regulations that restrict direct interactions between patients and drug companies. Source: newsinferno.com � 2009 NEWSINFERNO.COM (26/01/10)

Drugs may shut down several Epstein-Barr virus-induced diseases - possibilities for MS?

Tue, 26 Jan 2010 02:21:00 EST

The same virus that causes relatively mild mononucleosis, the "kissing disease," can also cause severe mono as well as several potentially deadly kinds of cancer. Now researchers think they can kiss a stealthy form of Epstein-Barr virus (EBV) goodbye - or at least shut it down enough to successfully treat several of the dangerous diseases it causes. Using a class of drugs being clinically tested to treat other kinds of cancer, researchers at the University of Wisconsin School of Medicine and Public Health found that the drugs were the first to stop the latent form of EBV infection from causing disease. The drugs, Hsp90 inhibitors, prevented human EBV-related tumors from growing in mice, protected immune cells from transforming into tumors and killed established tumor cells at low, non-toxic doses. Until now, there have been no effective drugs for treating latent EBV infection in any of the EBV-associated diseases, which in addition to mono include a subset of stomach cancers, certain types of nose-throat cancer and lymph node cancers such as lymphoproliferative disease, says lead author Shannon C. Kenney, MD. "This discovery suggests a new way of treating patients with severe mononucleosis, which in rare circumstances can be fatal, and patients with EBV-driven cancers, particularly immuno-compromised AIDS and transplant patients," says Kenney, an infectious disease expert at UW Hospital and Clinics. The study appears in the current (Jan. 25, 2010) Proceedings of the National Academy of Sciences. Kenney, also a professor of oncology at the McArdle Laboratory for Cancer Research and of medicine, has studied EBV for nearly 30 years. Most of her work has focused on the form of EBV that actively produces infection, but recently she turned to the so-called latent form. "The latent infection form actually is not so latent," says Kenney, a member of the UW Carbone Cancer Center. "This is the form of EBV that is most closely associated with cancer development." Latently infected cells express transforming viral proteins that can change normal cells into cancer cells. One key viral protein, EBNA-1, is required for EBV to live long-term in host cells. Many scientists and drug companies are looking for ways to block this viral protein, expressed in every EBV-infected cell. Kenney and her team had been using Hsp90 (heat shock protein 90) inhibitors as they studied the infectious form of EBV. "Normal cells can survive when treated with Hsp90 inhibitors," Kenney says. "In contrast, Hsp90 inhibitors are toxic to certain types of cancer cells, which often are more dependent upon high levels of Hsp90." After they discovered that EBNA-1 itself must have Hsp90 in order to function in cells, the Wisconsin researchers conducted three different experiments to see what the effect of exposing EBV-infected cells to Hsp90 inhibitors would be. In all three experiments, the results showed a dramatic reduction in EBNA-1-related activity. The drugs killed EBV-induced tumor cells in one experiment, halted the growth of EBV-induced tumors in mice in another and protected normal immune cells from becoming transformed to tumor cells in the third. And while the drugs were highly toxic to EBV-infected cells, they had very little effect on normal cells at the doses used in the experiments. The researchers found the underlying explanation to be that EBNA-1 could not be processed - synthesized and translated - to any degree when Hsp90 inhibitors were present. Kenney expects the inhibitors-geldanamycin, 17-AAG and 17-DMAG-may be useful for most but not all kinds of EBV-induced cancers as well as severe mono. In fact, the drugs may be even more widely useful, says Kenney, because clinicians are seeing that people older than age 70 are getting certain forms of EBV-induced cancers more frequently. "There also is tantalizing early evidence that EBV may contribute to auto-immune diseases such as lupus and multiple sclerosis," she says. And what about the possibilities for standard mono? "The majority of healthy humans will get over mono with no treatment after a month or two," says Kenney. "But Hsp90 inhibitors could potentially help, in terms of getting people back to school or work sooner. Clinical trials will need to be performed in patients to determine if these drugs are useful in severe mononucleosis." Source: PhysOrg.com � PhysOrg.com 2003-2009 (26/01/10)

European Medicines Agency issues recommendations following review of Tysabri and PML risk

Fri, 22 Jan 2010 03:13:00 EST

The European Medicines Agency has finalised a review of Tysabri (natalizumab) and the risk of progressive multifocal leukoencephalopathy (PML), a rare brain infection caused by the JC virus. The Agency�s Committee for Medicinal Products for Human Use (CHMP) has concluded that the risk of developing PML increases after two years of use of Tysabri although this risk remains low. However, the benefits of the medicine continue to outweigh its risks for patients with highly active relapsing-remitting multiple sclerosis, for whom there are few treatment options available. Because it is important that PML is detected early, the Committee recommended that a number of measures be put in place to ensure that patients and doctors are fully aware of the risks of PML. These include: * An update of the product information to add information about the increase in the risk of PML after two years of treatment and additional advice on how to manage patients who show signs of PML; * Forms to be signed by patients at the beginning of treatment with Tysabri, and again after two years of treatment, after in-depth discussions about the risk of PML with their doctor. Measures to minimise the risk of PML were part of the initial marketing authorisation for Tysabri, issued in June 2006. Since then, they have been continuously updated and strengthened to increase awareness of the risk of PML. The new measures are designed to complement the existing recommendations that patients, and their carers, partners and families should be made aware of the symptoms of PML and that patients should be closely monitored throughout treatment. Source: EMA (22/01/10)

BTG commences phase IIa study of Pleneva for Multiple Sclerosis

Thu, 21 Jan 2010 07:04:00 EST

BTG Plc said it commenced dosing in a European multicentre Phase IIa study of Pleneva, a novel orally administered compound under development as a potential treatment for multiple sclerosis. According to the company, the study, in 166 patients with the relapsing-remitting form of the disease, comprises an initial 24 week double-blind, placebo-controlled dosing period followed by a 24 week open-label extension. The primary endpoint of the study is a reduction in the number of new T1 gadolinium enhanced lesions on MRI at weeks 12, 16, 20 and 24 when compared to placebo. Source: RTT News � 2010 RTTNews (21/01/10)

Rewiring the brain with stem cells

Thu, 21 Jan 2010 06:30:00 EST

New research finds that in mice, transplanted neurons grown from embryonic stem cells can form proper connections with other brain parts. Writing in The Journal of Neuroscience, researchers described an experiment in which they successfully grew neurons from stem cells in Petri dishes, then transplanted those neurons into the brains of young mice. James Weimann, one of the authors of the study, said that the work was a hopeful sign for stem cell based treatments on the horizon. "These stem cell-derived neurons can grow nerve fibers between the brain�s cerebral cortex and the spinal cord, so this study confirms the use of stem cells for therapeutic goals," he said. However, the researchers cautioned that this work was so far only performed in young mice, and it remained to be seen whether the approach would work in older mice or in other animals. Source: Science Friday Copywrite ScienceFriday Inc. (21/01/10)

Biogen optimistic on Tysabri despite 3 new PML cases

Thu, 21 Jan 2010 06:10:00 EST

Biogen Idec officials said Wednesday three more patients have contracted a rare brain infection associated with the company�s multiple sclerosis drug, Tysabri. However, the Cambridge-based biotechnology company says the additional cases do not impact the overall safety profile for the medication. The total number of cases of progressive multifocal leukoencephalopathy, or PML, since July 2008 now stands at 31. More than 60,000 patients have taken Tysabri since the drug�s reintroduction in July 2006, and the incidence of PML is currently .47 cases per 1,000 patients. Tysabri�s warning labels said the anticipated incidence rate of PML is 1 in 1,000 rate. The company took Tysabri off the market between February 2005 and July 2006 because of concerns about the risk of PML. Since the risks of contracting PML increases the longer a patient takes the drug, the number of PML cases is expected to rise. So far, 19 cases have been detected in Europe, 10 cases in the United States. Two other cases have been detected elsewhere, according to Biogen officials. Source: Boston Business Journal � 2010 American City Business Journals, Inc (21/01/10)

New oral drug Cladribine for Multiple Sclerosis shows promise

Thu, 21 Jan 2010 05:42:00 EST

A major trial of the oral drug Cladribine � results of which are published in the New England Journal of Medicine on 20 January 2010 � has shown that it significantly reduces relapse and deterioration of the disease, and goes a long way to eliminating the unpleasant side effects associated with existing therapies. Cladribine is vying to be the first ever treatment in tablet form for MS, and only needs be taken for between 8 to 10 days a year, eliminating the need for regular injections and intravenous infusions otherwise endured by sufferers. The ease with which Cladribine tablets can be administered, combined with its relatively few side effects, make it a hugely exciting development in the world of MS. Multiple sclerosis is a disabling neurological condition which usually starts in young adulthood. It results from the body's own immune system damaging the central nervous system. This interferes with the transmission of messages between the brain and other parts of the body and leads to problems with vision, muscle control, hearing and memory. Cladribine tablets work by suppressing the immune system thus compromising its ability to further attack the central nervous system. Led by Professor Gavin Giovanonni at Barts and The London School of Medicine and Dentistry, the new study involved over 1,300 MS patients who were followed up for nearly two years and monitored using MRI scans. Patients were given either two or four short treatment courses of Cladribine tablets per year, or a placebo. Each course consists of one or two tablets per day for four or five days, adding up to just eight to 20 days of treatment each year. Compared to patients who were taking a placebo, those taking Cladribine tablets were over 55 per cent less likely to suffer relapse, and 30 per cent less likely to suffer worsening in their disability due to MS. Professor Giovanonni said: "The introduction of an oral therapy, particularly one that has no short term side effects and is as easy to use as oral Cladribine, will have a major impact on the treatment of MS. "However, the use of this drug as a first line therapy will have to be weighed up against the potential long term risks which have yet to be defined." Source: Queen Mary, University of London � Disabled World 2010 (21/01/10)

Low Vitamin D levels are associated with greater risk of MS relapse

Thu, 21 Jan 2010 04:53:00 EST

Low vitamin D blood levels are associated with a significantly higher risk of relapse attacks in patients with multiple sclerosis (MS) who develop the disease during childhood, according to a study conducted by researchers from the University of California, San Francisco. �We have known for some time that vitamin D insufficiency is a risk factor for developing MS, but this is the first study to assess whether vitamin D levels influence the disease course of those who already have MS,� said lead author Ellen Mowry, MD, MCR, a clinical instructor of neurology at the UCSF Multiple Sclerosis Center. The study, which is now published online by the �Annals of Neurology� and is available at http://www3.interscience.wiley.com/journal/123246501/abstract , demonstrates that an increase in vitamin D levels by 10 nanograms per milliliter of blood (ng/mL) corresponds with a 34 percent decrease in the rate of subsequent relapses. In other words, raising the vitamin D level of a person with MS by 15 ng/mL, which requires about 2,000 international units of vitamin D supplementation a day, could theoretically cut a patient�s relapse rate in half, explained Mowry. �Although we do not yet know if vitamin D supplementation will be beneficial for MS patients, the fact that there is a clear association between vitamin D levels and relapse rate provides strong rationale for conducting a clinical trial to measure the potential impact of supplementation,� she said. �This is an exciting finding because it indicates that it is very possible for vitamin D supplementation to have a profound impact on the course of this disease,� said senior author Emmanuelle Waubant, MD, PhD, an associate professor of neurology at UCSF and director of the Regional Pediatric MS Center at UCSF Children�s Hospital. Waubant said she expects similar findings in adult patients with MS. Multiple sclerosis is a chronic and often disabling disease that affects the central nervous system, which comprises the brain, spinal cord and optic nerves. A type of autoimmune disorder, MS causes the body�s own defense system to break down a substance called myelin, which surrounds and protects nerve fibers. Although MS occurs most commonly in adults, a small proportion of cases are diagnosed in children and adolescents. According to the National MS Society, two to five percent of all people with MS experience their first symptoms before the age of 18. The researchers measured vitamin D levels through blood samples from 110 patients whose MS symptoms began at age 18 or younger. The patients were seen at either UCSF Children�s Hospital or the State University of New York Stony Brook�s Regional Pediatric MS Center of Excellence � two of six multidisciplinary referral centers in the United States sponsored by the National MS Society. After providing the initial blood sample, patients were followed for an average of 1.7 years, during which the researchers recorded the total number of relapses each patient experienced. According to Mowry, a relapse or flare-up of MS causes new neurologic symptoms or the worsening of old ones, such as impaired vision, problems with balance, or numbness. Relapses can be very mild or severe enough to interfere with a person�s ability to function. During the follow-up period, the researchers assessed the patients� relapse rates and vitamin D levels after controlling for such factors as age, gender, race, ethnicity, use of MS treatments and the duration of follow-up care. �If we are able to confirm that vitamin D supplementation is an effective treatment, my hope is that it will help improve the quality of life for all MS patients,� Mowry said. In addition to a randomized clinical trial of vitamin D supplementation in MS patients, Mowry said further studies are also needed to determine the mechanism by which vitamin D affects inflammatory processes and, in turn, eases symptoms of MS. Additional co-authors from UCSF include Dorothee Chabas, MD, PhD; Jonathan Strober, MD; Jamie McDonald, BS; Jorge Oksenberg, PhD, and Peter Bacchetti, PhD. Co-authors from other institutions are Lauren Krupp, MD; Maria Milazzo, MS, CPNP, and Anita Belman, MD, all of the Pediatric MS Center, State University of New York at Stony Brook. The study was supported by a National MS Society Sylvia Lawry Fellowship Award and an additional grant from the National MS Society. Source: PRWEB (21/01/10)

Oral MS therapy FTY720 shows reduced risk of confirmed disability progression

Thu, 21 Jan 2010 02:37:00 EST

Results of the TRANSFORMS1 and FREEDOMS2 studies, the two pivotal Phase III clinical trials with oral FTY720 (fingolimod), have been published in The New England Journal of Medicine, providing comprehensive evidence to support the efficacy and safety profile of this first-in-class therapy for multiple sclerosis (MS). The data, from one of the largest Phase III programs conducted in MS, were included in the applications for regulatory approval submitted to the US Food and Drug Administration (FDA) and European Medicines Agency (EMEA) in December 2009. In both studies, two doses of FTY720 were examined (0.5 mg and 1.25 mg). Approval is sought for the lower 0.5 mg dose as the results from the studies indicate that this dose has the most positive benefit-risk profile. �Innovative science leading to new medicines for MS patients is greatly needed,� said John Richert, MD, Executive Vi ce President for Research and Clinical Programs at the US National Multiple Sclerosis Society. �The positive results published in The New England Journal of Medicine showing benefit of fingolimod on the clinical and MRI outcomes assessed is very encouraging for MS patients, their families and their physicians .� The one-year TRANSFORMS study involving 1,292 patients showed that oral FTY720 0.5 mg reduced relapses by 52% compared to interferon beta -1a (Avonex�)� given by intramuscular injection, while the reduction with FTY720 1.25 mg was 38% (both p<0.001). The two-year FREEDOMS study, involving 1,272 patients, showed that FTY720 reduced the relapse rate by 54% for the 0.5 mg dose and 60% for the 1.25 mg dose compared to placebo (both p<0.001). Patients on FTY720 0.5 mg also had a 30% lower risk of disability progression, three-month confirmed (p=0.02) and a 37% lower risk of disability progression, six-month confirmed (p=0.01) over two years compared to 2/4 placebo. Similarly, the FTY720 1.25 mg dose reduced the risk of three-month and six month confirmed disability progression by 32% (p=0.02) and 40% (p=0.006) respectively. In both studies, treatment with FTY720 also resulted in statistically significant reductions in brain lesion activity and reduced loss of brain volume as measured by magnetic resonance imaging (MRI). �The TRANSFORMS data demonstrate the efficacy of fingolimod compared to a current standard of care. These findings may represent a real step forward in the fight against MS,� said Jeffrey Cohen, MD, TRANSFORMS study lead investigator and staff physician at the Cleveland Clinic Mellen Center for Multiple Sclerosis Treatment and Research in Cleveland, Ohio, USA. �Current disease-modifying therapies for relapsing-remitting MS are administered by injection or infusion, which may negatively affect tolerability, convenience, and compliance for patients on these therapies.� Professor Ludwig Kappos, MD, principal investigator for the FREEDOMS clinical trial and Chair of Neurology and Research Group Leader in the Department of Biomedicine at the University Hospital in Basel, Switzerland, said: �FTY720 demonstrated clear clinical superiority over placebo in terms of reducing relapse rates and disability progression. The positive findings of TRANSFORMS and FREEDOMS give an increasingly complete understanding of the efficacy and safety of FTY720.� Up to 2.5 million people worldwide are affected by MS, an inflammatory and neurodegenerative condition that often begins when patients are in the prime of their lives 3. FTY720 has the potential to be the first approved therapy in a new class of drugs called sphingosine 1-phosphate (S1P) receptor modulators. These medicines reduce inflammation and may also have a direct beneficial effect on cells in the central nervous system (CNS). FTY720 acts selective ly by retaining certain lymphocytes (a sub-group of white blood cells) in the lymph nodes , reducing the number of lymphocytes that reach the brain where they can cause inflammatory destruction. This lymphocyte retention is reversible, allowing circulating lymphocytes to regain normal levels if treatment is stopped. �These data demonstrate that oral FTY720 has the potential to offer an important new treatment option for patients with MS,� said Trevor Mundel, MD, Global Head of Development at Novartis Pharma AG. �We have a long-term commitment to the MS community, and trust that FTY720, once approved, will prove to be a valuable treatment option for many people who live with this disease.� In both TRANSFORMS and FREEDOMS, adherence to therapy was best for the FTY720 0.5 mg and control groups compared to the 1.25 mg group. The most commonly reported adverse events for both FTY720 and control groups were nasopharyngitis, headache and fatigue. FTY720-related adverse events included dose-related, transient, generally asymptomatic heart rate reduction, infrequent transient AV conduction block, mild (1-3 mm Hg) blood pressure increase, macular edema (more common with 1.25 mg than the 0.5 mg target dose), and asymptomatic, reversible elevation of liver enzymes. The rates of infections overall, including serious infections, were comparable between treatment groups, although a slight increase in lung infections (primarily bronchitis) was seen in patients treated with FTY720. The number of malignancies reported in the two studies was small with comparable rates between the FTY720 and control groups; malignancies were reported more frequently with FTY720 than the control group in the one-year TRANSFORMS study but the opposite pattern was seen in the two-year FREEDOMS study.3/4 Serious adverse events were comparable between treatment groups, though generally slightly higher with the 1.25 mg than 0.5 mg dose. Overall rates of drug-related adverse events, particularly those related to the mechanism of action, as well as discontinuations due to adverse events , were more common with 1.25 mg than 0.5 mg. The completed MS FTY720 studies and their extensions include more than 2,300 patients with approximately 4,000 patient-years of exposure, including some patients now in their sixth year of treatment. Safety is also being monitored in approximately 1,000 additional patients in ongoing MS studies. The publication in The New England Journal of Medicine marks the first presentation of full results from the two studies. Top line results of FREEDOMS and TRANSFORMS have been disclosed in Novartis press releases, and the TRANSFORMS study has also been presented at scientific congresses 4. �Avonex� is a registered trademark of Biogen Idec. Dr. Jeffrey Cohen conducts research and is a paid consultant for Novartis. References 1 Cohen J. et al. Oral Fingolimod vs. Intramuscular Interferon in Relapsing Multiple Sclerosis. N Eng J Med. Vol.362 No.5, Feb 4, 2010 (printed version). 2 Kappos L, et al. Placebo-Controlled Study of Oral Fingolimod in Relapsing Multiple Sclerosis. N Eng J Med. Vol.362 No.5, Feb 4, 2010 (printed version). 3 National Multiple Sclerosis Society website. Last accessed Jan 15, 2010. 4 Cohen J. et al. Oral Fingolimod (FTY720) Versus Interferon Beta-1a in Relapsing-Remitting Multiple Sclerosis: Results from a Phase III Study (TRANSFORMS). Slide deck associated with Oral Presentation at the American Academy of Neurology Annual Meeting 2009. [S21.004]. Source: Novartis International AG (21/01/10)

Oral Therapy for Multiple Sclerosis � Sea Change or Incremental Step?

Thu, 21 Jan 2010 02:27:00 EST

Oral Therapy for Multiple Sclerosis � Sea Change or Incremental Step? William M. Carroll, M.B., B.S., M.D., F.R.A.C.P. The long-awaited arrival of oral formulations for the treatment of relapsing-remitting multiple sclerosis is welcome news for the estimated 2.5 million people worldwide who have this chronic, disabling disease. Since the publication of the first pivotal trial of interferon beta-1b in 1993,1 practitioners and patients alike have been anticipating the approval of oral therapies because of the relative ease of administration, which should improve adherence and reduce restrictions on lifestyle. In this issue of the Journal, researchers report the results of three well-conducted trials of the first two oral agents, cladribine and fingolimod, in the treatment of multiple sclerosis. The researchers studied cladribine in the Cladribine Tablets Treating Multiple Sclerosis Orally (CLARITY) trial2 and fingolimod in the FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) trial3 and the Trial Assessing Injectable Interferon versus FTY720 Oral in Relapsing�Remitting Multiple Sclerosis (TRANSFORMS).4 Although these two drugs differ in their mechanisms of action, both reduce the number of potentially autoaggressive lymphocytes that are available to enter the central nervous system. The articles, which report that the agents are effective and have manageable adverse-effect profiles, raise three questions: How do these therapies measure up against the existing treatments? Are all the longer-term adverse effects known? What do these drug trials tell us about multiple sclerosis and our treatment goals? Both cladribine (in the CLARITY trial) and fingolimod (in the FREEDOMS trial) were highly effective against placebo over a 2-year period, and fingolimod was more effective than intramuscular interferon beta-1a over a 12-month period (in the TRANSFORMS trial). Each of the three studies involved more than 130 centers in up to 32 countries, and the enrollments of 1272 to 1326 patients ensured that the trials were sufficiently powered to detect an effect of two doses of the active oral agent. Patients had active relapsing disease with durations of 7 to 9 years. On the Expanded Disability Status Scale (which ranges from 0 to 10, with higher scores indicating greater disability), patients had a median score of 2.0 in the fingolimod trials and mean scores ranging from 2.9 to 3.0 in the cladribine trial. All three studies used the annualized rate of relapse as the primary end point, and high and low doses of cladribine and fingolimod were shown to be superior to both placebo and interferon beta-1a. For cladribine versus placebo, the relative risk reduction in the annualized relapse rate was 57.6% for the group receiving 3.5 mg per kilogram of body weight and 54.5% for those receiving 5.25 mg per kilogram. For fingolimod versus placebo, the relative risk reduction was 54% for the 0.5-mg dose and 60% for the 1.25-mg dose. For fingolimod versus interferon beta-1a, the relative risk reduction was 52% for the 0.5-mg dose and 39% for the 1.25-mg dose. Both agents were superior to the comparators with respect to secondary end points, including measures on magnetic resonance imaging and a number of clinical end points, including the time to the progression of sustained disability at 3 months. Furthermore, although only fingolimod was tested against the widely used interferon beta-1a, it is likely that the two oral therapies will be at least as effective as other currently available disease-modifying therapies. In this regard, head-to-head trials of subcutaneous interferon beta-1b5 and interferon beta-1a6 versus intramuscular interferon beta-1a showed advantages of both subcutaneous regimens over the latter. More recent trials were unable to separate the clinical efficacy of the two subcutaneously administered forms of interferon beta from that of glatiramer acetate.7 Adverse effects were similar in all three trials of cladribine and fingolimod, and rates of events leading to discontinuation of a study drug were low but still at least twice as frequent with high-dose cladribine (7.9% for the 5.25-mg dose) and fingolimod (10% and 14% for the 1.25-mg dose). Herpetic infections occurred among patients receiving both cladribine and fingolimod. The rate of herpes infections among patients receiving the 1.25-mg dose of fingolimod was 5.5%; such infections were serious in three of these patients, two of whom died. Twenty cases of cutaneous herpes zoster were recorded among patients receiving cladribine, three of which were serious. Three solid tissue cancers (pancreatic, ovarian, and melanoma) occurred among patients receiving low-dose cladribine (3.5 mg per kilogram). Basal-cell carcinoma, melanoma, and breast cancer were all more common among patients receiving fingolimod than among those receiving interferon beta-1a. Macular edema was confirmed in 13 patients, 11 of whom received high-dose fingolimod (7 in the FREEDOMS trial and 4 in the TRANSFORMS trial). Of these 13 patients, 11 recovered within 1 to 6 months after discontinuation of therapy, and the condition of the other 2 patients stabilized. Transient bradycardia and first- and second-degree heart block occurred more frequently among patients receiving high-dose fingolimod than in the comparator groups. Lymphocytopenia was frequent in patients receiving both agents, more so with higher doses. Clinicians and patients will need to evaluate the risks and benefits of each of these drugs. Given the recent studies documenting the development of progressive multifocal leukoencephalopathy among patients receiving natalizumab, a monoclonal antibody against 4-integrin,8 close postmarketing surveillance will be important to detect any increase in these or other unexpected adverse effects. The mechanism of action of both oral agents represents a major change from those of currently available drugs for multiple sclerosis. Among a number of actions that are claimed for current therapies is that they change the emphasis of the immune response from activation of proinflammatory type 1 helper T cells to activation of antiinflammatory type 2 helper T cells. Even though cladribine is administered in two or four short courses annually, whereas fingolimod is given daily, both drugs were associated with persistent lymphocytopenia. Cladribine is resistant to the enzyme adenosine deaminase, which causes an accumulation of toxic deoxyribonucleotides in lymphocytes, resulting in relatively selective long-term depletion of CD4+ and CD8+ T cells.9 Fingolimod is a synthetic analogue of myriocin that is derived from a fungus (Isaria sinclairii). Once phosphorylated, the drug acts to down-regulate the sphingosine-1-phosphate receptor required for antigen-activated lymphocytes to egress, effectively locking them in the nodes.10 Thus, both cladribine and fingolimod are targeting inflammation, the key driver of immune injury in multiple sclerosis. Similarly, both natalizumab, which blocks lymphocyte access to endothelium in the central nervous system, and the anti-CD52 monoclonal antibody alemtuzumab, which destroys T and B cells, have shown impressive reductions in disease activity.11 Insights from these trials and others treating the initial stages of disease12 suggest that early direct targeting of the immune system offers the best hope for the prevention of later disability. The studies in this issue of the Journal provide a new horizon for patients with relapsing�remitting multiple sclerosis and a welcome increase in the range of treatment options. Although current therapies remain very effective, particularly when they are administered early, and have well-defined side-effect profiles, oral therapies further support a change in treatment approach to directly prevent immune-mediated injury. This approach will probably be followed until the next step in the therapeutic advance occurs, but such a change in strategy highlights the final question: What are the long-term goals of this new phase of therapy? The question will not be fully answered until the underlying cause of multiple sclerosis is better understood, but the lack of a definable end point remains a contentious issue for clinicians and health care funders alike. Time will determine the long-term effectiveness of these treatments in delaying the development of irreversible disability, and as ongoing, real-life experiments, they will contribute to our understanding of this enigmatic disease. References The IFNB Multiple Sclerosis Study Group. Interferon beta-1b is effective in relapsing remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology 1993;43:655-661. Giovannoni G, Comi G, Cook S, et al. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. N Engl J Med 2010. DOI: 10.1056/NEJMoa0902533. Kappos L, Radue E-W, O'Connor P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 2010. DOI: 10.1056/NEJMoa0909494. Cohen JA, Barkhof F, Comi G, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 2010. DOI: 10.1056/NEJMoa0907839. Durelli L, Verdun E, Barbero P, et al. Every-other-day interferon beta-1b versus once-weekly interferon beta-1a for multiple sclerosis: results of a 2-year prospective randomised multicentre study (INCOMIN). Lancet 2002;359:1453-1460. Panitch H, Goodin DS, Francis G, et al. Randomized, comparative study of interferon beta-1a treatment regimens in MS: the Evidence Trial. Neurology 2002;59:1496-1506. Achiron A, Fredrikson S. Lessons from randomised direct comparative trials. J Neurol Sci 2009;277:Suppl 1:S19-S24. Iaffaldano P, D'Onghia M, Trojano M. Safety profile of Tysabri: international risk management plan. Neurol Sci 2009;30:Suppl 2:S159-S162. Sipe JC. Cladribine for multiple sclerosis: review and current status. Expert Rev Neurother 2005;5:721-727. Massberg S, von Andrian UH. Fingolimod and sphingosine-1-phosphate -- modifiers of lymphocyte migration. N Engl J Med 2006;355:1088-1091. The CAMMS223 Trial Investigators. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med 2008;359:1786-1801. Goodin DS, Bates D. Treatment of early multiple sclerosis: value of treatment initiation after a first clinical episode. Mult Scler 2009;15:1175-1182. Source: The New England Journal Of Medicine (10.1056/NEJMe0912019) � 2010 Massachusetts Medical Society. (21/01/10)

Novel mouse model of demyelinating disorder

Mon, 18 Jan 2010 04:29:00 EST

In the February 1st issue of G&D, Dr. Brian Popko (The University of Chicago) and colleagues describe how mutation of a gene called ZFP191 leads to disordered CNS myelination in mice -- reminiscent of what is seen in human multiple sclerosis (MS) patients. MS is a chronic autoimmune disorder, in which the body attacks and destroys the myelin sheath that insulates and protects nerve fibers of the central nervous system (the brain, spinal cord and optic nerves). Demyelination disrupts the conduction of electrical impulses along nerve fibers, and results in regional neural deficits. MS symptoms range from tingling and numbness in limbs, to loss of vision and paralysis. It is estimated that MS affects 400,000 people in the US and approximately 2.5 million worldwide. Dr. Popko and colleagues identified a gene called ZFP191 as being necessary for the development of oligodendrocyte cells, which - in their fully mature form - produce myelin. The researchers found that mice harbouring a single mutation in ZFP191 display tremors and seizures, caused by a severe deficiency in CNS myelination. ZFP191 appears to be the first factor identified to be critical for the myelinating function of oligodendrocytes. The failure of Zfp191-mutant mouse oligodendrocytes to successfully myelinate their targets is reminiscent of human MS lesions, where re-myelination of damaged tracts fails to occur efficiently even when apparently mature oligodendrocytes are present in the area. While further research to delineate the precise targets of ZFP191 is needed, this work holds promising clinical value as a potential therapeutic pathway to promote re-myelination, reduce the accumulation of MS lesions and slow disease progression. Source: Medical News Today � 2010 MediLexicon International Ltd (18/01/10)

Pioneering surgery for MS clears British woman of disease symptoms

Sun, 17 Jan 2010 03:10:00 EST

Doctors believe they have cured a British woman of �multiple sclerosis after a pioneering operation. For years sufferers have been told there is no cure for MS, but the apparent success of the surgery has given new hope to those who are battling the disease, which attacks the nervous system. And Alex Gibbs is so certain she has now beaten the disease that she has even become pregnant � something she would never have dared do before. Alex, 38, travelled to the United States last June after reading on the internet about the breakthrough procedure, which involves widening the veins. She contacted surgeons in the UK and asked them to perform the surgery but none would agree. Alex, from Chelsea, West London, said: �I�ve only had MS since 2004. But I got it really badly right from the start. �I couldn�t walk more than 300ft without having to stop. I had stiff limbs and muscle spasms through the night in my sleep. �My future didn�t look very good having such �severe MS at the outset. Normally it worsens slowly. Within a couple of years I would probably have been in a wheelchair.� Many �experts believe MS is caused by a faulty immune system, but a number of �doctors now believe damage caused to the nervous system in MS is actually from poor blood flow in the chest, neck and head. One is Italian surgeon Paulo Zamboni, whose solution is to widen the veins using a �balloon or thin metal tubes. Alex had followed the work of Prof Zamboni, who cured his wife of MS five years ago and has now cured 100 more patients. As no UK doctors who specialise in MS are prepared to carry out Zamboni�s procedure until further studies are carried out, Alex went to �California, where a �surgeon at Stanford �University was willing to perform the �procedure. After the �5,000 op which widened her jugular veins, Alex�s symptoms improved immediately. Alex � whose mum died of MS at 68 � just months before she was diagnosed, reported back to her MS �consultant at the National Hospital in London. She said: �He�s not �convinced by Zamboni�s research, but he has accepted that my symptoms have �improved. And the lesions on my brain caused by the MS have not worsened.� Source: sundaymirror.co.uk � Mirror Group Newspapers 2010 (17/01/10)

European application for Fampridine-PR tablets to aid walking in Multiple Sclerosis submitted

Thu, 14 Jan 2010 02:58:00 EST

Biogen Idec has announced the submission of a marketing authorization application (MAA) to the European Medicines Agency for Fampridine Prolonged Release (Fampridine-PR) tablets, a novel oral therapy for the improvement of walking ability in adult patients with multiple sclerosis (MS). The company also has filed a New Drug Submission (NDS) to Health Canada. "Walking impairment has a significant impact on the lives of many people living with MS," said Alfred Sandrock, MD, PhD, Senior Vice President, Neurology Research and Development, Biogen Idec. "Fampridine-PR tablets may offer a novel approach to address this debilitating aspect of the disease by improving the walking ability of MS patients. We look forward to working with regulators to make this therapy available to people with MS in Europe and Canada." The MAA submission and Canadian NDS are based on a comprehensive development program including results from two Phase III, randomized, double-blind, placebo-controlled studies. These studies demonstrated the efficacy of Fampridine-PR tablets in improving walking ability in patients with relapsing-remitting, secondary progressive, progressive relapsing, and primary progressive MS. In the two Phase III clinical trials, a significantly greater portion (p<0.001) of Fampridine-PR-treated patients had a consistent improvement in walking speed when compared to placebo (34.8 percent vs. 8.3 percent and 42.9 percent vs. 9.3 percent, respectively). The increased response rate of the Fampridine-PR group was observed across all types of MS included in the studies. The Fampridine-PR treated subjects who had consistent improvement in the two studies experienced an average increase in walking speed of 25.2 percent and 24.7 percent compared to 4.7 percent and 7.7 percent, respectively, for the entire placebo group. The majority of the study participants in these trials were using immunomodulatory drugs, including interferons, glatiramer acetate, and natalizumab; however the magnitude of improvement in walking ability was independent of concomitant therapy. Source: Biogen Idec (14/01/10)

Tysabri sales top $1 billion, new patients grow 30 percent

Wed, 13 Jan 2010 07:08:00 EST

Biogen Idec Inc. said sales of its multiple sclerosis drug Tysabri topped $1 billion in 2009, and there were 30 percent more new patients taking the drug. The growth comes as the rate of a potentially fatal side effect in patients taking Tysabri remains a lingering concern for Wall Street. In 2005, the drug was pulled from the market because of concerns over a potentially fatal brain infection called progressive multifocal leukoencephalopathy, or PML. Sales resumed in July 2006 with restrictions, though about two dozen cases have since been reported, mainly abroad. In 2009, sales reached $1.06 billion, with $508.5 million in the U.S. and $550.7 million internationally. A key concern has been that fears of the brain infection could bog down the addition of new patients. At the end of 2009, there were 48,800 patients taking Tysabri worldwide, including 24,500 in the U.S. and 23,700 internationally. An additional 600 patients were taking the drug in clinical trials. Several analysts said the rate of new patients adding the drug is slowing. Leerink Swann analyst Dr. Joshua Schimmer said about 2,600 started taking the drug during the fourth quarter, down from more than 2,900 in the third quarter. But he said much of the concern is already included in outlooks for the company. He reaffirmed an "Outperform" rating on the stock and said Tysabri revenue is in line with Wall Street expectations. Looking ahead, the company has said it will focus on accelerating growth of Tysabri and its top seller, the multiple sclerosis drug Avonex. Source: San Francisco Examiner copyright SF Newspaper Company 2010 (13/01/10)

Could multiple sclerosis by caused by blocked veins?

Tue, 12 Jan 2010 05:03:00 EST

Five years ago, opera singer Joan Beal had one of those life-changing shocks when her husband Jeff was told he had multiple sclerosis. She and Jeff, an Emmy-award-winning musical director, had been married for more than 20 years and the news came as a huge blow. The diagnosis was bad enough, but just as distressing was that the treatment - anti-inflammatory drugs and chemotherapy - was aimed only at reducing symptoms. What Joan wanted to know about was the underlying cause. 'Jeff was really sick by the time he agreed to see the doctor,' she says. 'He was numb on his left side and his feet were burning. When they ran tests on him, he also had signs of liver damage and little blood spots all over his shins and ankles. 'When I asked the neurologist why he was so sick, she said Jeff needed to stop drinking. That was flippant and made me angry because Jeff didn't touch alcohol.' The encounter sent Joan off on a search for a better approach, and in May Jeff became one of the first in the world to have a new and controversial operation based on a radical theory about the cause of MS. Seven months later, the improvement has been dramatic. 'Jeff had immediate and profound relief of very severe fatigue,' says Joan. 'Before the op he had trouble getting out of bed and needed naps during the day. Since then, he has had no MS attacks (when symptoms get much worse). He still has leg pain, spasms and headaches, but these are less than before.' So, has Joan Beal discovered an effective treatment for MS? MS affects around 100,000 people in the UK. The conventional view is that it's an auto-immune disease, like rheumatoid arthritis. For some reason, the body turns against itself and starts destroying the myelin, the insulating fatty layer around nerve cells in the brain and spinal cord. This affects how messages are transmitted in the brain, causing the classic symptoms of MS, including vertigo, numbness, temporary vision loss and crushing fatigue. It can also cause paralysis and incontinence. Jeff's operation was inspired by a new theory about why the myelin gets destroyed - it's thought MS is a disease of the blood vessels, specifically the veins. The doctor at the forefront of this approach is Dr Paolo Zamboni, a professor at the University of Ferrara in Italy. He began investigating MS when his wife Elena, 51, developed the disease ten years ago. He examined MS patients with ultrasound and found that in nearly all, the veins leading from the brain had signs of narrowing, twisting and blockage; something he didn't find in healthy patients. He saw that blockages were allowing iron from the blood to leak into the brain tissue, where it causes damage. Dr Zamboni called the condition chronic cerebrospinal venous insufficiency (CCSVI). He calculated that by clearing the blockage in the main neck vein, he could help reverse MS symptoms. To do this, he used a technique known as angioplasty - inserting a tiny balloon into the blocked vein and then blowing it up to open up the blood vessel. It is a standard procedure for expanding the arteries of heart patients. By the time Joan found out about Dr Zamboni, he'd operated on 65 MS patients - including his wife, who is symptom free three years after surgery. Of those, 50 per cent were 'relapse-free' for at least 18 months compared with only 27 per cent in a control group who didn't have the operation. Inspired by his findings, Joan contacted one of the top cardiology experts in the U.S. who has pioneered the use of stents - another standard procedure opening blocked arteries - and sent him reports of Professor Zamboni's work. He agreed to scan the veins in Jeff's neck. 'When we saw Jeff's mangled veins on the MRI scan,' says Joan, 'our doctor was amazed. He said he'd never seen this in the jugular veins before. The left one was closed 95 per cent, the right 80 per cent.' Just why the veins get blocked isn't clear. Dr Zamboni believes it could be a structural problem that is present from birth. Jeff had stents put into his neck veins at Stanford University hospital in California. After describing the success of Jeff's operation on an internet MS bulletin board (thisisms.com), Joan was inundated with requests for more information. And the cardiologist was swamped with requests for the operation. So much so that he has asked for his name to be withheld. But in the past seven months he has operated on 70 MS patients and many of them have posted reports on the website. One wrote: 'Less spasticity in left leg; facial pain is gone; right side back pain is gone; normal sweating; high altitude headaches gone; walking gait is smoother. No progression since intervention.' But the accounts don't gloss over the potential side-effects of the operation; these include nerve damage that stents can cause and bleeding in the stomach as a result of drugs used in the operation. So is this a breakthrough in the treatment of MS? Dr Robert Zivadinov, leading a study for more evidence at Buffalo University in New York, says: 'If we can prove the hypothesis that CCSVI is the underlying cause of MS, then it is going to change the face of how we understand the disease.' But the theory has attracted criticism. Dr Alasdair Coles, an academic neurologist at Cambridge University, says: 'We know MS is an auto-immune disease because if you block the immune response with drugs, people get better.' Dr Susan Kohlhaas, of the UK MS Society, adds: 'Our experts don't accept that blockages to draining veins from the brain are specific to people with MS or that this explains the cause of MS.' There have been many false dawns in MS research. The cause of the damage has been linked with lack of vitamin D, lack of the hormone prolactin, mercury fillings and now CCSVI is added to the list. Joan and many others pray that it's not another example of offering false hope. Source: Daily Mail � Associated Newspapers Ltd (12/01/10)

Wedge-shaped medullary lesions in multiple sclerosis suggestive of an impairment of venous drainage

Mon, 11 Jan 2010 04:30:00 EST

Multiple sclerosis (MS) is a heterogeneous disease with variable clinical features and magnetic resonance imaging (MRI) findings. We report four MS cases with unusual wedge-shaped lesions in the paramedian ventral medulla oblongata demonstrated on MRI. The clinical features and MRI characteristics of the medullary lesions suggest an impairment of venous drainage. We propose that the formation of these wedge-shaped lesions may be related to the pattern of venous drainage in the ventral medulla and raised venous pressure due to chronic cerebrospinal venous insufficiency which has recently been described in MS. Qiu W, Raven S, Wu JS, Carroll WM, Mastaglia FL, Kermode AG. Centre for Neuromuscular and Neurological disorders, University of Western Australia, Australia; Department of Neurology, Sir Charles Gairdner Hospital, Queen Elizabeth II Medical Centre, Perth, Western Australia, Australia; Department of Neurology, the Third Affiliated Hospital of Sun yat-sen University, Guangzhou, China. Copyright � 2010 Elsevier B.V. All rights reserved. Source: PubmedPMID: 20056253 (11/01/10)

Additional $860,000 grant for oral Estriol Multiple Sclerosis clinical trial announced

Mon, 11 Jan 2010 03:30:00 EST

Adeona Pharmaceuticals, Inc., has announced that the ongoing clinical trial of its Trimesta� (oral estriol) drug candidate being conducted by Dr. Rhonda Voskuhl, Director, UCLA Multiple Sclerosis Program, UCLA Dept. of Neurology has received an additional $860,440 in grant funding through the American Recovery and Reinvestment Act. The current phase II/III clinical study is a double-blind, placebo-controlled trial taking place at sixteen sites in the US and will enroll up to 150 female Multiple Sclerosis (MS) patients. Investigators will administer Trimesta along with glatiramer acetate (Copaxone�), an FDA approved therapy for MS, to women between the ages of 18-50 who have been recently diagnosed with relapsing-remitting MS. This ongoing clinical trial previously received a $5 million grant from the National Multiple Sclerosis Society (NMSS) in partnership with the National MS Society's Southern California chapter, with support from the National Institutes of Health (NIH). According to Dr. Voskuhl, "This additional funding has already had a very positive impact on our trial. It has greatly increased the rate of enrollment by supporting the addition of 9 more clinical sites, bringing the total up to 16 sites across the US. We were extremely pleased that our trial was deemed important enough to be supplemented with these additional funds." Previous Phase II Clinical Trial Results in Relapsing Remitting Multiple Sclerosis Trimesta (oral estriol) has previously completed an initial 22-month, single-agent, crossover Phase I/II clinical trial in the US for the treatment of MS in relapsing remitting patients, with highly encouraging results. The results showed the total volume and number of enhancing pathogenic myelin lesions (established neuroimaging measurements of disease activity in MS) decreased during the treatment period as compared to a six-month pretreatment baseline period. The median total enhancing lesion volumes decreased by 79 percent (p=0.02) and the number of lesions decreased by 82 percent (p=0.09) within the first three months of treatment with Trimesta. Following a six-month drug holiday during which the patients weren't on any drug therapies, Trimesta therapy was reinitiated during a four-month retreatment phase of this clinical trial. The relapsing-remitting MS patients again demonstrated a decrease in enhancing lesion volumes of 88 percent (p=0.008) and a decrease in the number of lesions by 48 percent (p=0.04) compared with original baseline scores (1),(2). Improvement in Cognitive Testing Scores During the prior Phase I/II clinical trial, a 14-percent improvement in Paced Auditory Serial Addition Test ("PASAT") cognitive testing scores (p=0.04) was also observed in the MS patients at six months of therapy. PASAT is a routine cognitive test performed in patients with a wide variety of neuropsychological disorders such as MS. The PASAT scores were expressed as a mean percent change from baseline and were significantly improved in the relapsing-remitting group. About the Trimesta Phase II/III Study In the current phase II/III study, Trimesta is being given orally once-a-day versus placebo to 150 female relapsing-remitting MS patients in combination with a standard of care background therapy, subcutaneously injected glatimer acetate. The primary endpoint for the study will evaluate effects of the treatment combination on relapse rates at two years with a one year interim analysis using standard clinical measures of MS disability as well as secondary endpoints of magnetic resonance imaging measurements of brain lesion and effects on cognition. The study is approaching 50% enrollment with the rate of enrollment benefiting significantly from the expansion of clinical sites. Source: Adeona Pharmaceuticals, Inc (11/01/10)

Progesterone can shield brain from injury and possibly demylienation

Wed, 30 Dec 2009 04:14:00 EST

Progesterone, a hormone that increases tenfold during pregnancy, is thought to help the developing fetus by protecting it from oxidative stress and aiding neuron development. But a growing body of research leads some doctors to think it could also be a useful first-line treatment after a traumatic brain injury (TBI) or stroke. In an article published in the January issue of the American Journal of Roentgenology, researchers argue that a spate of recent studies have shown that the hormone might be the first compound after 30 years of testing to protect the brain during acute-stage TBI. And if given to patients in time, the hormone might protect cognitive function and even save lives. In a recent phase 2 clinical trial with 100 subjects sponsored by the National Institute of Neurological Disorders and Stroke, researchers say patients with moderate-to-severe brain injuries given the hormone intravenously for three days were more than twice as likely to survive: mortality rates were around 14 percent for the hormone versus about 30 percent for placebo. Another recent study, this one in China with 159 patients, had similar results. And while the doctors don't know if the findings will apply to humans, work on rats with strokes caused by blocked middle cerebral arteries has shown better brain function following the attack if given the hormone. This is critical because currently only about 3-5 percent of stroke patients can be treated with tissue plasminogen activators (tPA), a blood thinner that breaks up clots and the only real first-line treatment for strokes currently used. The reason most stroke victims can't get the drug is that doctors have to be absolutely certain the patient is suffering a stroke, otherwise it could cause deadly internal bleeding. And to work, it has to be administered within the first 3� hours. Progesterone, by contrast, has shown no adverse effects in any of the studies, and appears to have a wide window, about 24 hours, in which it can work. How it works "It's a hormone, in my opinion, that's evolved to protect the fetus," says Donald Stein, Ph.D., a researcher at Emory University and the lead author of the paper. "A lot of mechanisms in repair, not only in the brain but in all highly traumatized tissue, while not identical in development are similar." The hormone, which can cross the blood-brain barrier, appears to protect neurons in a variety of ways, by preventing injured brain cells from committing suicide and also by blocking the agents that break down their myelin sheaths. But perhaps most critically, it seems to prevent one of the main dangers of brain trauma: swelling. "One of the things about swelling in the brain, called cerebral edema from, say, injuries in the battlefield, is...that it can kill somebody if not controlled," says Dr. Stein. "And what progesterone has been shown to do effectively is to basically dramatically reduce inflammation and subsequently swelling," he says. On top of all this, progesterone and its army of metabolites also interfere with glutamate production, a neurotransmitter that floods regions following a trauma. Glutamate, along with other brain chemicals released in injury, can help overexcite the brain and lead to post-traumatic epileptic seizures. That's why progesterone is sometimes given to women with certain forms of seizures to prevent the triggering of debilitating neuronal "electric storms." Future studies But how well the hormone really holds up in preventing lasting damage following TBI will be revealed soon. Dr. Stein says a NINDS-sponsored phase 3 double-blind randomized trial, running at 17 centers and expected to handle upwards of 1,200 patients, should start next month. Source: DOTmed.com �2001-2009 DOTmed.com, Inc.(30/12/09)

Shine On Scotland now campaign to fortify school milk with Vitamin D

Wed, 30 Dec 2009 03:00:00 EST

When 14 year old Ryan Mclaughlin started his Shine on Scotland campaign he had set a goal to get vitamin D into our school milk, a simple idea to protect every child in scotland from Multiple Sclerosis, but he quickly became aware that far more diseases would benefit from vitamin D supplementation not just MS. Now the country's largest private health care provider BUPA agree�s and says we should all be taking between 1,500 to 2,000 IUs per day to beat cancer. This is 5 times the current UK RDA and exactly what Ryan has campaigned tirelessly for almost 9 months. Dr Virginia Warren, assistant medical director for Bupa, commented: �There has been a lot of research over the last few years about the health benefits of taking a vitamin D supplement. Based on this evidence, we would recommend taking between 37.5 and 50 micrograms of vitamin D on a daily basis to help reduce your risk of certain cancers. Spending time outside in summer will also increase your vitamin D levels, but is a risk for skin cancer. "Ensuring you get enough vitamin D is a simple and effective way to reduce your risk of developing certain cancers. Alongside this, it�s important to ensure you eat a healthy balanced diet, exercise regularly, only drink in moderation and do not smoke." It was again reinforced today when the Israeli Health Ministry announced that all 3% milk is to be fortified with vitamin D in the next 3 months and Ryan McLaughlin wants the Scottish Government to look to follow suit. Last week on a STV news interview with Ryan McLaughlin in relation to his win for vitamin D campaign he said �that fortification of school milk was still at the top of his priorities� as he still thinks its the best way to protect future generations of Scots from many diseases not just MS, this announcement by the Israeli Government only goes to further back his case and show that it can be done on a national basis and with the worst health record in western world and the highest rates of MS in the world � Scotland must take the lead. Dr Sareeram Ramagopalan of Oxford University and Ryan�s family all gave evidence at the Scottish Parliaments petitions committee back in June and told the committee that Israel was looking at fortification of both Milk and flour and we heard that France was also looking at it, now its been confirmed in Israel we need to really start considering moving towards fortification of the school milk program now in scotland. There are many problems associated with just offering supplementation, simply try getting a child to take a supplement every day for their young life seems doomed for failure, Ryan says he has forgotten a few times to take his and he is running the vitamin D camapign! How many adults get a course of antibiotics which state finish the course and don�t. Ryan says �I am sure almost every adult can say that take them till they feel better and the rest is left in a medical cabinet�. Furthermore do we really want kids popping tablets everyday? Can we ask our teachers to dish out supplements he doesn't think so. We would need to ask the questions from the Education Dept, teachers and of course get the teachers unions to agree to it, teachers have a big work load already, Ryan points out that many parents will be able to relate to the following point? How many times as a parent have you been called home and had to take a day off work when a paracetamol would sorted a sore head or a slightly high temperature and the child could have stayed in school getting educated � It would all take too long, too many problems to overcome. We could spend millions of pounds trying to educate parents and expectant mothers to take vitamin D supplements everyday, but I believe we should lead from the front from the start , we owe it to the kids and we must protect each and every child in Scotland. If parents don�t want it for their kids � let them simply opt out! Ryan believes we need to think much much bigger! He think we should educate parents to the idea of the benefits of vitamin D everyday and proposing putting vitamin D into the school milk programme so kids get it every day, start debating it with the public and informing parents immediately. Vitamin D boosts your immune system to help fights off cold and bugs and it would improve the school attendence records on wasted days of school due to simple sniffles, as well as save parents the loss of earnings by taking time off work with sick kids that could be in school learning. Add his very valid points to the figures compiled for national supplementation of vitamin D in Scotland in relation to just MS alone and you have very good case � Scientists believe it could prevent 2000 cases over 10 years in Scotland alone and could save the UK economy some �4.5 billion surely children�s health must be the priority and a penny onto the cost of a pint of milk is well justified and we should start talking to the dairies immediately! Source: Shine On Scotland (30/12/09)

Proof of principle clinical trial of ATX-MS-1467 for Multiple Sclerosis

Thu, 24 Dec 2009 02:00:07 EST

Apitope International NV, the autoimmune peptide therapy company, and Fast Forward, LLC, the National Multiple Sclerosis Society's subsidiary devoted to bridging the gap between research and drug development, today announced a partnership to support Apitope's proof of principle clinical trial of ATX-MS-1467. This peptide therapeutic vaccine is designed to target and prevent the abnormal pathological immune response in multiple sclerosis (MS). The agreement with Apitope is the first in a series of partnerships between Fast Forward and early stage biotechnology companies. "We are pleased to partner with Apitope to accelerate the development of innovative therapies for MS," said Dr. Timothy Coetzee, Fast Forward's Executive Director. "ATX-MS-1467 has the potential to redirect the immune system in MS which is essential to minimizing the damage to the nervous system in this highly debilitating disease." Adds Dr. Coetzee "We are concerned about the small number of therapies in development for MS relative to other diseases and the impact that the current economic climate will have on development of new treatments for people with MS. Fast Forward is committed to reversing this trend by deploying its resources to spur development of innovative MS therapies and bring them to market as quickly as possible............." For the full report please go to MSRC: MS Research News : Drugs : ATX-MS-1467

Evaluation of the safety and efficacy of sildenafil citrate for erectile dysfunction in men with Multiple Sclerosis

Wed, 23 Dec 2009 10:00:11 EST

The etiology of multiple sclerosis (MS)-emergent erectile dysfunction (ED) is still matter of debate, since both organic and psychological factors have been implicated. There is an association between sexual dysfunction (SD) and destructive lesions in the pons, in MS patients. Central and peripheral nerves systems play a key role in the erectile process. The innervation of the penis is both autonomic (sympathetic and parasympathetic) and somatic (sensory and motor). Pudendal nerves have a central role in erection. Tactile stimulation of the penile shaft activates parasympathetic fibers, which travel in the pudendal nerve and function through the spinal reflex arc from S2 to S4. Neural signals originating in the brain are transmitted to a thoracolumbar erection center and trigger the psychogenic erection associated with either fantasy or viewing erotic material. In addition, the ischiocavernosus and bulbospongiosus striated muscles, which located at the penile crus, are innervated by the motor pudendal nerve. Contraction of these muscles has a definite, contributory role in penile erection. Therefore, erection is a neurovascular event, and any disease or dysfunction affecting the brain, spinal cord, or cavernous and pudendal nerves can induce ED. With respect to placebo, sildenafil produced a 16% greater success rate for vaginal penetration, and a 15% greater rate for successful intercourse. For satisfaction with erection hardness, and satisfaction with the sexual experience, sildenafil did not produce two-fold greater rates. For all efficacy variables, sildenafil had similar or slightly greater scores compared with placebo................. For the full report please go to MSRC: MS Research News : Drugs : Viagra (sildenafil)

Welsh government called upon to follow Scottish in vitamin D deficiency awareness

Tue, 22 Dec 2009 02:12:00 EST

The Welsh Assembly Government has been called upon to fund a campaign about vitamin D deficiency and multiple sclerosis. The MS Society Cymru is calling for ministers to follow Scotland�s lead and raise awareness about the links between the two. Such a campaign would encourage pregnant women and children under four to take a regular vitamin D supplement. Scientists recently discovered that MS could be prevented through daily vitamin D supplements.There is a clear link between vitamin D � known as the sunshine vitamin � and a gene that increases the risk of MS, raising the possibility that the debilitating auto-immune condition could be eradicated. The prevalence of MS is far higher in typically wet and cold countries such as Wales, where 110 people in every 100,000 are living with the condition. In a country with lots of sunshine � such as Brazil � only 18 people in every 100,000 have MS. The NHS in Scotland said it would raise awareness about the links between vitamin D deficiency and MS this month, after being spurred into acting by Glasgow teenager Ryan McLaughlin. Ryan�s mother, Kirsten, has had MS for three years, and Ryan, 14, has shown some symptoms of the disease but the family only discovered the link earlier this year after a family holiday. The teenager said: �I was shocked there had not been publicity around this before. We wanted there to be more awareness of the link and more research into how much of a problem it is in Scotland.�These actions will make a big difference � it will go a long way to giving children some protection against the disease and give parents proper advice.� Joseph Carter, spokesperson for MS Society Cymru, said: �We are delighted by this announcement by the Scottish Government and are now calling on the Welsh Assembly Government to do the same.�You are 10 times more likely to develop MS in Rhyl than you are Rio de Janeiro, and new research suggests this is due to vitamin D deficiency.� Vitamin D, obtained from foods and through the action of sunlight on skin, is essential for maintaining healthy bones.It is unclear exactly what causes MS but it has become increasingly evident that environmental and genetic factors play a role. Previous research has shown that populations from Northern Europe have an increased MS risk if they live in areas receiving less sunshine.This supports a direct link between deficiency in vitamin D, which is produced in the body through the action of sunlight, and increased risk of developing the condition. Researchers at the University of Oxford and the University of British Columbia this year discovered a direct relationship between the genetic variant DRB1*1501, which is associated with MS, and vitamin D. Dr Julian Knight, a co-author of the research, said: �In people with the DRB1 variant associated with MS, it seems that vitamin D may play a critical role.�If too little of the vitamin is available, the gene may not function properly.� And the study�s lead author Dr Sreeram Ramagopalan said: �Our study implies that taking vitamin D supplements during pregnancy and the early years may reduce the risk of a child developing MS in later life.� A spokeswoman for the Welsh Assembly Government said: �We are working closely with the MS Society to raise awareness of multiple sclerosis.�Earlier this year, we produced a leaflet, Multiple Sclerosis � living with a long term condition. This includes information on the condition, its symptoms and the people affected.� Source: Shine On Scotland (22/12/09)

Epstein-Barr virus may cause Multiple Sclerosis through involvement of the venous system

Sun, 20 Dec 2009 03:32:00 EST

Possible connection to Chronic Cerebrospinal Venous Insufficiency (CCSVI) explained. Re: Epstein�Barr virus is associated with grey matter atrophy in multiple sclerosis R Zivadinov, M Zorzon, B Weinstock-Guttman, M Serafin, A Bosco, A Bratina, C Maggiore, A Grop, M A Tommasi, B Srinivasaraghavan, M Ramanathan J Neurol Neurosurg Psychiatry 2009;80:620-625 Published Online First: 23 January 2009 doi:10.1136/jnnp.2008.154906 Dear Editor, I read the article by Zivadinov (1) with reference to the association of Epstein-Barr virus (EBV) to gray matter atrophy in multiple sclerosis (MS) patients. Accumulation of EBV infected B cells in meninges and perivascular regions of MS lesions in 21 or 22 patients with MS (2) was noted as well, indicating direct involvement of the brain and perivascular spaces by EBV in MS patients.. A recent study has indicated chronic cerebrospinal venous insufficiency with multiple extracranial venous strictures in MS patients (3). EBV appears to infect endothelial cells (4), and may be important in the pathology of EBV virus. EBV virus has been found to cause deep venous thrombosis in a patient with hereditary thrombophilia (5). EBV may infect the venous endothelium causing venous thromboses and strictures in the cranial and spinal venous drainage system and perivascular regions of MS lesions in patients with MS. Such venous involvement may be implicated in MS disease involvement. Chronic EBV infection may involve the venous system with secondary effects on the brain and spinal cord in MS. References 1.Zivadinov R, Zorzon M, Weinstock-Guttman B, Serafin M, Bosco A, Bratina A, et al. Epstein-Barr virus is associated with grey matter atrophy in multiple sclerosis J Neurol Neurosurg Psychiatry 2009; 80: 620 -625. 2.Serafani B, Rosicarelli B, Franciotta D, et al. Dysregulated Epstein-Barr virus infection in the multiple sclerosis brain. J Exp Med 2007; 204:2899-2912. 3. Zamboni P, Galeotti P, Menegatti E, Malagoni AM, Tacconi G, et al. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2009: 80: 392-398. 4. Jones K, Rivera C, Sgadari C, Franklin J, Max EE, et al. Infection of human endothelial cells with Epstein-Barr virus. J Exp Med. 1995; 182: 1213-1221. 5. Mashav N, Saar N, Chundadze T, Steinvil. Epstein-Barr virus associated thromboembolism: A case report and review of the literature. Thromb Res. 2008; 122: 570-571. No conflict of interest. Steven R Brenner, Neurologist St. Louis VA Medical Center and Dept Neurology and Psychiatry at St. Louis University Source: J Neurol Neurosurg Psychiatry � 2009 by the BMJ Publishing Group Ltd

Tysabri - Multiple Sclerosis patient with progressive multifocal leukoencephalopathy has died

Sat, 19 Dec 2009 09:00:02 EST

A multiple sclerosis patient who developed a severe brain infection after taking Biogen Idec Inc. and Elan Corp.'s Tysabri, the fourth case reported in five months, has died, according to Biogen. Cambridge, Massachusetts-based Biogen was informed of the American woman's death two days ago, company spokeswoman Naomi Aoki said in an interview. The company reported on Oct. 29 that the patient had been diagnosed with the brain illness, progressive multifocal leukoencephalopathy. Tysabri, which generated $597 million in sales in the first nine months of the year, is Biogen's second-best-selling medicine after the MS drug Avonex. Biogen and its marketing partner, Irish drugmaker Elan, pulled Tysabri from the market in February 2005 after three patients, two of whom died, contracted PML. The death is the first among four cases of the brain illness reported since the drug was reintroduced in the U.S. in 2006........................... For the full report please go to MSRC: MS Research News : Drugs : Disease Modifying Drugs : Disease Modifying Drugs Ongoing News : TYSABRI�

Multiple sclerosis drug Tysabri may reduce immunity

Sat, 19 Dec 2009 05:00:02 EST

A drug used to treat multiple sclerosis might make some patients vulnerable to brain infection by reducing the number of immune cells there, researchers at UT Southwestern Medical Center have found. The findings also suggest that the drug, natalizumab, might be safer and more effective when given with treatment "holidays" instead of continuously over long periods, the researchers said. "Natalizumab is very effective in keeping pro-inflammatory cells out of the brain to reduce damage from MS," said Dr. Olaf Stuve, the assistant professor of neurology at UT Southwestern and senior author of the study, which appears in the December issue of Archives of Neurology. But the potential downside is interference with immune surveillance against infection, he said. Thus, infections of the brain or spinal cord may go undetected until they become a serious problem. "However, our study has limitations because of the small number of autopsies that were involved," "Whether or not treatments other than prolonged, uninterrupted dosing may benefit patients with MS should be tested in controlled clinical trials," Dr. Olaf Stuve said................... For the full report please go to MSRC: MS Research News : Drugs : Disease Modifying Drugs : Disease Modifying Drugs Ongoing Research : TYSABRI� Ongoing Research

Possible MS breakthrough neglected by American media

Fri, 18 Dec 2009 05:03:00 EST

by Erika Milvy Folks who suffer from Multiple Sclerosis are not really a rowdy bunch. Activism and outrage are hard to muster for the chronically fatigued. But since Thanksgiving, people with MS and their loved ones have gone all ACT-UP 2.0. That is, the past few weeks have seen a surge in online activity within the MS community - as bloggers, vloggers and forum posters are calling one another to action in response to the lack of response to what many perceive to the scientific breakthrough they've been waiting for. If you haven't heard about the report in December's Journal of Vascular Sciences by Italian vascular surgeon Dr. Paolo Zamboni, then you probably live in America. I don't suffer from premature ejaculation but I do know, (thanks to the New York Times), that there's a new drug for it available in nine countries, but that it hasn't yet been approved for sale in the United States. But when I went looking for news about Dr. Zamboni's research, I could not find it the mainstream press. I did find it all over the Canadian Press and European Press. Let me start by saying I am not a doctor nor do I play one on TV. On November 21, CTV W5 (Canada's top television network), aired an in-depth story about "a stunning new discovery of a revolutionary new treatment for a debilitating disease." They interviewed Dr. Paolo Zamboni, from the University of Ferrara in northern Italy. His research suggests that MS is not, as widely believed, primarily an autoimmune condition, but a vascular disease (CCSVI, short for chronic cerebrospinal venous insufficiency.) Dr. Zamboni found that, in over 90 percent of people with Multiple Sclerosis, the veins draining blood from the brain were constricted and this led to a buildup of iron in the brain that, he theorized, causes the neurological symptoms of MS. MS would therefore be caused by a drainage problem, a plumbing clog that Zamboni posits can be rectified with a simple but experimental surgical technique similar to an angioplasty. Zamboni (and up until last week, a doctor at Stanford) have since done the procedure on over 100 patients and Zamboni reports vast improvement in patients' symptoms nearly immediately. Zamboni's wife, Elena Zamboni was one of his first success stories - her MS being his driving force. Since then, a battle between patients and practitioners has hit the net. Fervor has collided against skepticism and medical cynicism - and media disregard has stirred up resentment and even conspiracy theories. Patients' blood (whether it is or is not circulating adequately in the veins) has been boiling. It began after the Canadian television aired their interview with Dr. Zamboni. The broadcast went swine viral. Avis Favaro, the reporter who broke the story, said that she has been "shocked at the tremendous response to this story. It is beyond that for any other medical story we have worked on." The segment has been linked to countless times worldwide and translated into other languages." The web was ablaze. People with MS finally heard the word "breaththrough" and heard the long long-awaited announcement of what was a potentially paradigm shifting game changer. These were not just mice getting better. "My legs don't work, but I'm jumping up and down," said one hopeful MS patient on YouTube. So when the videos and links arrived in the inboxes of MS patients in the U.S. they looked to the reputable news media for more information. But still the mainstream press wasn't reporting the story. On ThisIsMS.com, an MS info-exchange, postings about CCSVI topped 16,000, (other treatment news numbers in the tens or hundreds.) In online forums, discussions turned to "where is the coverage on this?" "No one will listen" is the title of one long thread. A Facebook group called "MS Uprising" was born, a YouTube channel was born. The MS society of Canada crafted a statement of cautious optimism. They adapted a "wait and see stance, urging patients to "temper their euphoria." Web activists were not satisfied and began to draft petitions and suggest diverting donations to directly support hospitals like University of Buffalo where Zamboni's approach is being further studied. Of the MS society's statement, Dr. Lorne Brandes, an oncologist who blogs for CTV News' Health Blog, wrote, "If their official response to Dr. Zamboni's research was any cooler, icicles would form on their spokespersons' lips. Why am I not surprised? These organizations are big money operations, run by risk-adverse professionals and fundraisers who are absolutely petrified of making a mistake and prematurely backing a losing horse. Their interests are also heavily intertwined with those of Big Pharma." This sentiment is echoed again and again. Online articles scream out with Woodward and Bernstein-wannabee headlines like "Simple Surgical Cure for Multiple Sclerosis Opposed by Big Pharma" and "Multiple Sclerosis cure found, MS societies in panic" - (but the article's content is just a reprint of The Globe and Mail's less provocatively titled "Researcher's labour of love leads to MS breakthrough." But when bloggers and vloggers and posters invoke "Big Pharma," they start sounding like they think they're Ralph Fiennes in "The Constant Gardener" - blowing the whistle on the industry's evils. Still, when newly radicalized sick people notice that the media isn't reporting on this big story and notice that neurologists and advocacy organizations are minimizing or denigrating the importance of Zamboni's findings, their conspiracy theories start to sound sort of plausible. That is, just because they're paranoid doesn't mean that Big Pharma isn't out to get them. The pharmaceutical industry stands to lose a lot if Zamboni's one-time treatment pans out. The most common drug therapies for MS cost about $30,000 a year. And there are well over 100 medications for various MS symptoms. On one MS forum is a link to another pharma-gate headline: "Big Pharma's Crime Spree", in which the reporter for Bloomberg Markets Magazine assesses that "finding cures is not even remotely a consideration by pharmaceutical executives." While this idea is not a new one, when you pair it with the recent directives from the MS Society (well-funded by the drug industry) patient distrust doesn't seem unwarranted. The Canadian MS Society urged patients "not to abandon the treatment they are on." The US went further, discouraging patients from getting tested at all. Prescribing ignorance is bad advice. At best it's condescending. Much of the medical establishment's approach seems to be likewise paternalistic. Some patients have concluded that naysaying neurologists are territorial - MS is their disease. And if Zamboni is right, MS researchers have been barking up the wrong tree for decades. Bloggers gripe that the US scientific establishment is mired in red tape and is overly-concerned about malpractice. So some have already undergone experimental surgery. With degenerative disease breathing down their necks, some patients are ready to pursue even a glimpse of a cure, damning the torpedoes. Which alarms many of their doctors. Who rain on their parade. Which causes more suspicion and activism. Dr. Elizabeth Crabtree, a neurologist at UCSF's MS Center, has plans to begin an ongoing podcast to better inform MS patients of new developments. So they don't have to learn it on the streets, as it were. "No wonder there's so much distrust," she said. "The treatment options are inadequate." She expressed frustration that medical facilities compete instead of collaborate. Patients, doctors and support groups should be working in alliance, she said. Whether egos and money do get in the way of out-of-the-box thinking, one cautionary tale does loom. A patient at Stanford died following CCSVI surgery recently and another patient underwent open heart surgery after a stent migrated to his heart. The Stanford program was swiftly halted. Dr. Michael Dake's "under the radar" stent implants (Zamboni uses a "balloon" procedure ) were conducted before a clinical trial. But instead of being deemed unethical, Dr. Dake was called a hero and a "pioneer" in online groups. "This I would do," said Dayle Baich of the Zamboni procedure. Baich, who now uses a walker because of her MS, told The Ottawa Citizen, "it's a very simple surgery, compared to two years of chemotherapy. In three years, I have gone from being normal to now. So where am I going to be in two or three more years? I don't have the time. Neither do most of the people here." As a direct result of patient activism, the MS Society has announced plans to fund CCSVI research and clinical trials will commence at several medical centers in 2010. CBS and other esteemed news outlets have caught wind of the whirlwind. Their coverage is due out soon. Such is the story of keyboard activism - among the "handicapable" (a term the TV show "Glee" recently coined.) In case Ralph Fiennes is looking for his next project. Source: The Huffington Post � 2009 HuffingtonPost.com, Inc (18/12/09)

Multiple sclerosis incidence in the Faroe Islands 1986�2007

Thu, 17 Dec 2009 02:48:00 EST

Joensen P. Multiple sclerosis incidence in the Faroe Islands 1986 - 2007. Objective - Epidemiological studies of the isolated Faroese population in 1945 identified a high annual incidence of multiple sclerosis (MS) of 10/100,000. At the time, there was speculation that the disease was brought to the country by British occupation forces resident in the islands from 1940 to 1945. The objective of the current study is to determine the incidence of diagnosis of MS in the Faroe Islands during the period 1986 - 2007. Methods -All patients in the Faroe Islands diagnosed with MS from July 1, 1986 to July 1, 2007 are documented in the current longitudinal, prospective study. The diagnosis is based on clinical observation, magnetic resonance imaging scanning, cerebrospinal fluid tests, and visual evoked potential response testing. Results -The incidence of MS during the period 1986 - 2007 is 4.5/100,000 annually. This is generally of the same order of magnitude as other research findings in Scandinavia and Iceland. The incidence of MS from 1986 to 2007 is about double the incidence in the Faroe Islands for the period from 1940 to 1986, calculated to be 2.7/100,000 annually. Conclusion -The observed incidence of MS in the Faroe Islands, where the population is genetically homogeneous and where the diet exposes the population to neuro-toxic contamination, is at the same level as found in other high-risk regions. The former detected epidemics of MS in Faroe Islands seems apparently to have leveled out and could not be recognized in the recent period covered by the present survey. Source: Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2009.01252.x.� 2009 The Author Journal compilation � 2009 Blackwell Munksgaard.(17/12/09)

University of British Columbia plans to test potentially groundbreaking MS treatment

Wed, 16 Dec 2009 05:50:00 EST

The University of British Columbia has announced plans to begin patient trials to test a potentially groundbreaking method of diagnosing and treating multiple sclerosis, a disease that afflicts up to 75,000 Canadians. Researchers have proposed launching a study involving 100 patients to test a theory that MS is a vascular disease that can be treated with surgery. It's the first research proposal in Canada to suggest evaluating the findings of an Italian doctor whose early studies indicate that multiple sclerosis might be caused by vein blockages that lead to a buildup of iron in the brain. The findings of Paolo Zamboni have generated a great deal of interest among researchers and those with MS. Earlier this year, the Multiple Sclerosis Society of Canada appealed to scientists to follow up Dr. Zamboni's theories. The proposed UBC trial, which would be done in collaboration with researchers at the University of Saskatchewan, is an answer to that appeal, said Anthony Traboulsee, medical director of the UBC MS Clinic. Dr. Traboulsee said Dr. Zamboni's studies have caused both hope and anxiety among people with MS. They are hungry for a breakthrough, but realize the Italian doctor's findings are preliminary. �They are very anxious about this,� Dr. Traboulsee said Tuesday in an interview. �MS is a lifelong disease. Young people are hungry for hope.� Because of the intense interest in the new findings, Dr. Traboulsee said the proposed patient trials must �take a careful� approach. Unlike Dr. Zamboni's earlier studies, the UBC research plan will include a control group � which gives more heft to a study's findings � and will take place over a longer period. In Dr. Taboulsee's proposed trial, researchers would closely examine participants' neck and stomach veins. The study group will include people with and without MS. Each participant will undergo three tests, including an ultrasound, a magnetic resonance imaging test and the insertion of a catheter. In that test, dye is injected to give researchers a closer look at the veins. Only MS participants with blocked or narrowed veins will move on to the second stage of the trials. Half that group will undergo a vein dilation procedure � similar to an angioplasty � to expand the vein, the other half won't. The purpose of UBC's proposed research trial is to build on the knowledge uncovered by Dr. Zamboni, a professor of medicine at the University of Ferrara in Italy. His theory is that a condition that he dubbed chronic cerebrospinal venous insufficiency causes MS. The current thinking is that MS is an autoimmune condition in which the immune system attacks myelin, a fatty substance that coats nerve cells. Dr. Zamboni found that, in about 90 per cent of people with multiple sclerosis, the veins draining blood from the brain were malformed or blocked, which led to a buildup of iron in the brain, which he theorized causes the neurological symptoms of MS. Dr. Zamboni had 65 of his patients undergo an angioplasty to clear the blockage. Of those, 50 per cent reported no attacks in the next 18 months. In a group that did not have surgery, that rate was 27 per cent. Multiple sclerosis is a degenerative condition that can cause loss of balance, heat sensitivity, impaired speech, double vision and paralysis. UBC's trial still needs funding and approval from an ethics committee. The researchers will apply for funds from the MS Society of Canada, private donors and the Canadian Institutes of Health Research. Dr. Taboulsee said the study will cost nearly $1-million for equipment and staff. Researchers including some at UBC have already been studying links between MS and iron in the brain, Dr. Taboulsee said. He said the latest findings are like another piece to a jigsaw puzzle. Previous studies have linked MS to, among other things, a Vitamin D deficiency and cold climates. Source: The Globe And Mail � 2009 CTVglobemedia Publishing Inc. (16/12/09)

Genetic variant associated with Multiple Sclerosis risk may also be linked to number of spinal cord lesions

Wed, 16 Dec 2009 05:06:00 EST

Multiple sclerosis (MS) afflicts the central nervous system, causing unpredictable and varying symptoms that differ from person to person. About one in 700 people in the United States is affected by the disease. Although there is currently no cure for MS, there are treatments that can slow the progression of the disease and enhance the quality of life for people who have this condition. Researchers have identified several genetic variants in the HLA region of the genome �an area containing many genes involved in immune system function � that seem to affect MS symptoms, disease severity, and response to treatment. One of these variants is in the HLA-DRB1 gene. Known as HLA-DRB1*1501, this variant is associated with increased risk for MS, though exactly how it is involved in development of the disease is unclear. In a report published online today in the journal Archives of Neurology, a team of researchers led by Drs. Madeleine Sombekke and Chris Polman of Vrije University in Amsterdam uncovered a clue which may elucidate the connection between the HLA-DRB1*1501 variant and multiple sclerosis. They analyzed *1501 and other genetic variants in 150 Dutch individuals with multiple sclerosis to see if any of the SNPs were associated with variation in brain and spinal cord lesions. One SNP in particular, rs3135388 (used as a proxy for HLA-DRB1*1501), was associated with spinal cord lesions. People carrying at least one copy of the A version of rs3135388 had significantly more spinal lesions and had more segments of the spinal cord affected than people with two copies of the G version. MS is believed to be an autoimmune disorder � wherein the immune system attacks the body�s own cells rather than foreign invaders � and so it makes sense that genetic variants in immune system genes would influence the course of the disease and its clinical features. HLA genes, in particular, encode proteins that contribute to self vs. non-self immune recognition. Previous studies have proposed a link between HLA-DRB1*1501 and disease severity. Since lesions on the spinal cord are often used to diagnose MS and the degree of disability, Sombekke�s team suggests that the association of HLA-DRB1*1501 with spinal cord lesions might help explain its relationship with severity of the disease. Source: The Spittoon Copyright � 2009 All Rights Reserved 23andMe (16/12/09)

Stem cells 'reverse' Multiple Sclerosis in Canberra man

Tue, 15 Dec 2009 02:32:00 EST

A Canberra man diagnosed with multiple sclerosis (MS) just over 12 months ago appears to be on the road to recovery after being treated with stem cells. Ben Leahy was in a wheelchair earlier this year and had suffered partial vision loss in one eye, but has since recovered to the point where he is walking. The 20-year-old's remarkable recovery came after he underwent a procedure in which stem cells were harvested from his bone marrow, before chemicals were used to destroy all his existing immune cells. Mr Leahy's stem cells were then re-injected. ACT neurologist Dr Colin Andrews said the treatment appeared to have reversed the effects of MS which Mr Leahy was diagnosed with in August 2008. Dr Andrews said Mr Leahy still had mild weakness in his right leg and some visual loss in one eye, but appeared to be recovering well. "At the moment, there's a good chance we may have arrested the disease," he told ABC News. The treatment, which carried a risk of death of eight per cent several years ago, was performed in Sydney after Dr Andrews was unable to get the green light from peers in Canberra. It has also given hope to other sufferers of the disease. Dr Andrews said the treatment offered between a 60 per cent and 80 per cent chance of halting the disease in some patients and a good chance of reversing it in others. Almost 20,000 Australians have MS, which affects the central nervous system, prevents nerve impulses from travelling to the brain, spinal cord and eyes. While the treatment appears to have reversed the progress of the degenerative disease in Mr Leahy, there is no cure. Source: smh.com.au � 2009. Fairfax Digital (15/12/09)

Cervical cancer vaccine Gardasil possibly linked to MS episodes

Sun, 13 Dec 2009 05:15:00 EST

THE cervical cancer vaccine Gardasil has triggered multiple sclerosis (MS) symptoms in some girls after being inoculated. Doctors said the victims were either teenagers or women in their early 20s who may have been predisposed to MS or who had a prior history of symptoms. St Vincent's Hospital neurologist Dr Ian Sutton reported five cases in a journal article in January. Another five have since emerged. "Gardasil vaccination is not the cause of MS; whether or not it was a trigger for episodes of inflammation in the brain in these rare cases is unclear," Dr Sutton said. All cases were in women aged under 26, the target group of a vaccination program that began in 2007. Symptoms began within three weeks of vaccination and lasted from weeks to months. "We have raised the question: has the vaccine modified what may have occurred anyway or just been an additional trigger?" Dr Sutton said. The Therapeutic Goods Administration (TGA) last week said six million doses of Gardasil � created by scientist and former Australian of the Year Ian Frazer � had been distributed in Australia, and 1476 suspected adverse reactions had been reported to the regulator. "The TGA is also aware of a small number of cases in which neurological symptoms, similar to those experienced in patients with a dedemyelinating disorder such as multiple sclerosis, have been reported shortly after HPV (human papillomavirus vaccination)," the regulator said. The cases involving neurological symptoms have been investigated by an independent panel. The vaccine has been tested on more than 30,000 women worldwide, its manufacturer CSL said. "In spite of reports of some neurological symptoms occurring after vaccination, when those have been investigated no causative relationship with the vaccine has been determined," company spokeswoman Rachel David said. Source: Couriermail.com.au � 2009 Queensland Newspapers. (13/12/09)

IV ocrelizumab shows promise in phase II study in relapsing-remitting Multiple Sclerosis

Thu, 10 Dec 2009 11:29:00 EST

Roche and Biogen Idec announced that the experimental monoclonal antibody ocrelizumab, given intravenously, significantly reduced disease activity as measured by MRI (magnetic resonance imaging) scans in a phase II study of 220 people with relapsing-remitting MS. Ocrelizumab binds to a molecule (CD20) on the surface of B cells and depletes them from the circulation. B cells are immune cells that make antibodies and may play a role in the immune attack on brain and spinal cord tissues in multiple sclerosis. The drug is a humanized version of rituximab, a mouse antibody to CD20 that has previously shown benefit in people with relapsing-remitting MS. In the aspects of this phase II study participants were randomly assigned to receive one of two treatment regimens and observed for 24 weeks, with plans for observing them for up to 96 weeks. Participants received repeated intravenous infusions of one of three different dose regimens of ocrelizumab or inactive placebo) or intramuscular injections of Avonex�. The main objective of this study was to determine whether ocrelizumab was effective in reducing MS disease activity compared with placebo, as observed on MRI at 12, 16, 20, and 24 weeks. The companies report that ocrelizumab "showed a strong effect with a highly statistically significant reduction" in signs of disease activity. The companies are continuing to analyze the data, and plan to provide a full report at an upcoming medical meeting, including the results of secondary endpoints - which include relapse rate and the appearance of new disease activity - and safety information. Since this was a phase 2 study, additional research will be needed to further determine this drug's safety and efficacy. Source: MSS Canada (10/12/09)

Biogen Idec's oral compound BG-12 achieves development milestones in MS and RA

Wed, 09 Dec 2009 12:08:00 EST

Biogen Idec announced that its oral compound BG-12 (dimethyl fumarate) achieved key milestones in clinical trials for multiple sclerosis (MS) and rheumatoid arthritis (RA). In recent months, the last patient was enrolled in the CONFIRM trial, the second of two Phase III trials designed to evaluate the efficacy and safety of BG-12 as a monotherapy in patients with relapsing-remitting multiple sclerosis (RRMS). Both the DEFINE and CONFIRM Phase III trials are now fully enrolled and will evaluate the effect of BG-12 on clinical relapse, disability progression, various MRI measures of disease activity, and safety. The last patient was also enrolled in a Phase II study to evaluate the safety, tolerability and efficacy of BG-12 in combination with methotrexate in subjects with active RA who had an inadequate response to conventional disease-modifying antirheumatic drug (DMARD) therapy. "There is significant unmet need in both the MS and RA communities for additional treatment options," said Kate Dawson, M.D., senior director, Medical Research, Biogen Idec. "The Phase IIb study of oral BG-12 in patients with MS showed promising MRI results regarding the compound's ability to reduce inflammation and its potential for neuroprotection. We look forward to results from the DEFINE and CONFIRM Phase III MS studies, as well as the proof-of-concept trial in RA." BG-12 has been shown to activate the Nrf2 transcriptional pathway, which pre-clinical studies have shown defends against oxidative-stress induced neuronal death, protects the blood-brain barrier and supports maintenance of myelin integrity in the central nervous system. Central nervous system inflammation and damage may trigger the symptoms common in RRMS such as fatigue, cognitive deterioration and physical disability. Because of BG-12's unique effect on the Nrf2 pathway and its oral delivery, BG-12 is also being considered for future MS combination therapy studies. Additionally, as an oral compound, BG-12 holds promise for patients with RA. Its combination of anti-inflammatory and potential cytoprotective properties support the compound's evaluation in RA. BG-12 is an oral formulation of dimethyl fumarate. Fumaderm�, a therapeutic for the treatment of psoriasis in Germany, includes dimethyl fumarate as one of the active ingredients. Fumaderm has more than 14 years of post-marketing experience and approximately 100,000 patient years of use. About DEFINE and CONFIRM DEFINE (Determination of the Efficacy and safety of oral Fumarate IN rElapsing-remitting MS) is a two-year, randomized, double-blind, placebo-controlled, dose-comparison study of 240 mg BID or TID of BG-12 orally compared to placebo in 1,200 patients with RRMS. CONFIRM (COmparator and aN oral Fumarate In Relapsing-remitting MS) is a two-year, randomized, placebo-controlled and active reference comparison study in more than 1,400 patients with RRMS. In the three-arm study, patients are randomized to 240 mg BID or TID of BG-12 orally, placebo capsules orally, or 20 mg of Copaxone� (glatiramer acetate) via subcutaneous injection. These Phase III, global, multi-center trials are being conducted in more than 300 centers in N. America, Europe and throughout the world. Source: Medical News Today � 2009 MediLexicon International Ltd (09/12/09)

Endovascular treatment of cerebrospinal venous insufficiency safe, may provide benefit in MS

Mon, 07 Dec 2009 10:57:00 EST

New data from a pilot open-label study suggest that endovascular treatment of strictures in extracranial cerebrospinal veins is safe in patients with multiple sclerosis (MS) and may provide some neurological benefit for these patients, researchers conclude. The controversial approach, which has recently been making headlines in consumer media outlets, proposes that narrowing in the veins draining the brain, called chronic cerebrospinal venous insufficiency (CCVI), may be an early step in the disease process causing MS, and further, this narrowing may respond to simple angioplasty. Lead author Paolo Zamboni, MD, director of the Vascular Diseases Center at the University of Ferrara, Italy, emphasized that the current report should be viewed as an interesting finding that urgently requires replication by other groups. "What we know is that MS is very complex and multifactorial," Dr. Zamboni told Medscape Neurology. "We have identified an unknown factor and possible treatment for this factor." The study is published as an online article in the December issue of the Journal of Vascular Surgery. CCVI and MS In a previous study published online in December 2008, Dr. Zamboni and colleagues assessed venous outflow routes in 65 patients with clinically definite MS (CDMS) and 235 control patients using a combined transcranial and extracranial color Doppler high-resolution examination. They reported that CDMS and venous outflow abnormalities were "dramatically" associated, with an odds ratio of 43 (95% confidence interval, 29 - 65; P < .0001). Venography showed the presence of multiple severe extracranial stenoses affecting the principal venous segments in the patients with MS but not the control patients. "This provides a picture of chronic cerebrospinal venous insufficiency with 4 different patterns of distribution of stenosis and substitute circle," the authors write. "Moreover, relapsing-remitting and secondary progressive courses were associated with CCVI patterns significantly different from those of primary progressive (P < .0001)" (Zamboni P, et al. J Neurol Neurosurg Psychiatry 2009;80:392-399). In an editorial accompanying that publication, Claude Franceschi, MD, from Saint Joseph and Piti�-Salp�tri�re Hospitals in Paris wrote that, "in light of the association between such a previously overlooked vascular picture and MS, a further stimulating research field is opened by this article. This should be addressed in understanding the contribution of venous drainage to the different aspects of inflammation, autoimmunity and neurodegeneration characterising the intriguing puzzle of MS" (Franceschi C. J Neurol Neurosurg Psychiatry 2009;80:358). Dr. Zamboni stressed that this association between venous stenoses in main extracranial veins and MS is not contradictory to what is already known about the disease. "What I've found is a previously unknown factor, widely diffuse in my MS population, which could trigger or facilitate both immune reaction and inflammation," he told Medscape Neurology. "If you have elevated pressure and difficulty of drainage in the brain, you have the possibility of extravasation of blood components crossing the blood�brain barrier, and this could trigger inflammation and also immune reaction." Restenosis a Problem In the current report, the researchers describe the safety and early outcomes in these same patients after endovascular treatment of stenoses in the internal jugular vein and the azygous vein. Of the 65 patients, 35 had relapsing-remitting disease, 20 had secondary-progressive disease, and 10 had primary progressive MS. All underwent percutaneous transluminal angioplasty to address strictures in these veins. All procedures were done as day surgery under local anesthesia, and no operative or postoperative complications were seen, including vessel rupture, thrombosis, or adverse effects from contrast. Postoperative headache was reported in 6 patients, which resolved spontaneously, and minor hemorrhages with hematoma occurred at vascular access sites "occasionally," the authors report. After the procedure, venous pressure was significantly lower in the internal jugular and azygous veins (P < .001). Stenoses in these venous pathways "were never found to be isolated," the researchers note, but always combined in the internal jugular, azygous veins, or lumbar system in 4 main patterns of distribution. At a mean follow-up of 18 months, the risk for restenosis after intervention was higher in the internal jugular vein, Dr. Zamboni noted, with a patency rate of 53% compared with 96% in azygous veins (95% confidence interval, 3.5 - 72.5; P < .0001). Patency at follow-up depended on the type of obstruction faced, including membranous obstructions, twisting, and hypoplasia. A stent was placed in 1 patient to resolve a twisted vein, but a second case not treated with a stent retwisted, the authors note. Using the patients as their own control, the researchers found improvement with treatment on some clinical outcome measures after the intervention, particularly for the relapsing-remitting patients. In this group, 27% were relapse-free before surgery and 50% were so after treatment (P < .001). Gadolinium-enhancing lesions on magnetic resonance imaging (MRI) fell from 50% to 12% on a blinded assessment (P < .001). Significant improvement over the preoperative assessment was seen at 1 year on the Multiple Sclerosis Functional Composite again for relapsing-remitting patients (P < .008), but not among those with a secondary or primary progressive course. Physical quality-of-life measures also improved significantly in relapsing-remitting MS patients and in primary-progressive patients, with a positive trend among those with secondary progressive disease. Mental quality of life also was significantly improved for the relapsing-remitting and primary progressive groups, but not for those with secondary progressive MS. The authors conclude that although improved endovascular techniques are needed to approach the internal jugular vein, "the results of this pilot study warrant a subsequent randomized control study." It is possible that the addition of stents to this endovascular approach that he calls the "liberation procedure" may improve outcomes, Dr. Zamboni noted. "However, the results are really interesting, if you think that all treated patients were already under the best treatment for MS and had adjunctive neurological benefits from the liberation procedure compared to the previous 2 years." Mixed Response From Neurology Community Asked for comment on these findings, Lily Jung, MD, from the Swedish Neuroscience Institute, Seattle, Washington, speaking on behalf of the American Academy of Neurology, was cautious in her assessment. She feels some of the strong claims in the current report are not supported by the data. For example, the number of patients in the report is small, "and to make the correlation between the patterns of venous obstruction and the categories of MS is a real stretch," Dr. Jung said. Assessment was done by unblinded neurologists, which is "not ideal." She also noted that the MRI results used different techniques, different protocols, and different study intervals. "The bottom line is that my colleagues and I have been flooded by calls and emails from patients who have been led by the publicity around this article to believe that there is a cure for MS, and to make such a claim with such preliminary results is premature," Dr. Jung said. "We would welcome some randomized, controlled, double-blinded studies to look at the issue, but before then would not be encouraging our patients to jump in with both feet to do this procedure, which has significant risks and has not been proven to be safe." As a vascular interventionalist, Dr. Zamboni says he is keen to collaborate with neurologists in the setting of MS, but acknowledged that his work has had a mixed response from the neurology community. Some, he says, have been excited and at least curious, which in his view is important in research. Researchers from institutions including Stanford, Harvard, SUNY Buffalo, and others have asked to discuss the technique so that they may attempt to reproduce these findings in their own populations. "To the contrary, of course, I've also found big opposition, but I think that probably it is a prejudgement, and they have not read the paper carefully," he said. "But it's not important. What is important is to have other people interested in doing the research and understanding more." The first step will be to understand how widespread the presence of CCVI is among patients with MS, he said. "We need to test patients very rapidly to have the epidemiological data, which are very important." Already, Dr. Zamboni is collaborating with Robert Zivadinov, MD, and colleagues at Buffalo General Hospital in New York on an open-label, MRI-blinded study of 16 relapsing-remitting patients with MS with confirmed strictures in the cerebrospinal venous outflow routes. Half � 4 randomly selected patients in Italy and 4 in New York � will undergo early intervention to address the blockages at 3 months, and 8 patients will have a delayed procedure at 6 months of follow-up. Safety and preliminary efficacy will be monitored using MRI and clinical examination, and outcomes will be compared at 1 year. Dr. Zamboni and Dr. Zivadinov presented their protocol at the 25th Congress of the European Committee for the Treatment and Research in Multiple Sclerosis earlier this year in D�sseldorf, Germany. In Buffalo, Dr. Zivadinov is also conducting a larger epidemiological study aimed at determining the prevalence of CCVI among their MS patients. Dizzying Excitement, Desperate Hope Although Dr. Zamboni has published previously on this procedure, a news report by a national Canadian news organization with an associated documentary on the same network recently profiled this work, generating a dizzying excitement for many patients in Canada, where MS rates are among the highest in the world. Their subsequent comments on various Internet news and patient sites reflect a desperate hope that this new approach may provide those with MS a possible alternative to lifelong drug therapy and the steady encroachment of disability. In a public statement issued December 1, the National Multiple Sclerosis Society cautioned that the findings are preliminary. "Many questions remain about how and when this phenomenon [CCVI] might play a role in nervous system damage seen in MS, and at the present time there is insufficient evidence to prove that this phenomenon is the cause of MS." However, the society also notes that it is very interested in seeing more data on this procedure and is prepared to put its money where its mouth is, calling for research proposals to generate that data. "If confirmed, these findings may open up new research avenues into the underlying pathology of MS, as well as potential new approaches to therapy," the statement notes. "The National MS Society has invited research proposals to investigate this lead, and is in active discussions with the MS Society of Canada about the possibility of collaborative funding of [CCVI] research." The authors have disclosed no relevant financial relationships. Source: Medscape Today � 1994-2009 by Medscape (07/12/09)

Could Novartis be first to launch Multiple Sclerosis oral therapy?

Mon, 07 Dec 2009 03:55:00 EST

Novartis AG is jockeying with German drug maker Merck KgaA to deliver the first disease modifying treatment for relapsing forms of multiple sclerosis that can be taken orally, rather than by infusion or injection. Fingolimod could finally move ahead in the race to market, as the FDA rejected Merck's new drug application for its Cladribine tablet. On November 30, US regulators issued a "refusal to file letter" to Merck Serono, the US subsidiary. Company spokesman Gangolf Schrimpf told me the FDA preliminary action of the cladribine submission was not an assessment of the efficacy and safety of the compound. Nonetheless, the agency obviously felt the deficiencies in the filing were material enough - scientific or legal - to delay its formal review of the tablet. Initial results from Novartis' two-year FREEDOMS FTY-720 study show that once-daily oral fingolimod reduced the relapse rate by 54 percent for the 0.5 mg dose in patients with relapsed MS. Novartis looks to file its new drug application with the FDA within next few months, followed fast track approval and launch in summer 2010. Though efficacy over standard-of-care beta interferon treatments is similar for the two oral agents, I suspect that neurologists' prescribing behaviours might be more favourably disposed towards cladribine, which offers a more convenient - a short-course regimen - five-day dosing, twice a year. Merck's setback is thus Novartis' gain, as it affords a window of time for providers - and patients - to gain clinical experience with fingolimod therapy. In my opinion, the FDA being circumspect about cladribine did have more to do with safety than efficacy. Abnormal low blood levels of white blood cells (called lymphopenia) and four cases of malignant tumors were reported in cladribine-treated patients in the pivotal CLARITY trial. No surprise, as the drug reduces circulating levels of white blood cells (lymphocytes, which are involved in the pathogenesis of MS) and inhibits DNA synthesis and repair (parenteral cladribine was approved as a chemotherapeutic for Hairy Cell Leukemia back in the 1990s). Concerns exist, too, that cladribine can affect the immune system many years after cessation of treatment. Merck Serono would not answer my question on whether or not the rejection had to do with the company's post-marketing safety protocol, its Risk Management and Mitigation Strategy (RiskMap). "We will work closely with the FDA to fully understand FDA's concerns and define a path forward for a successful resubmission of this application at the earliest point in time," is all spokesman Schrimpf would diplomatically say. No disease-modifying agent is without risk. Fingolimod, first in a new class of immunomodulatory drugs called S1P-receptor modulators, also reduces circulating levels of white blood cells (by bottling them up in lymph nodes). Skin cancer is a risk associated with fingolimod treatment. The FDA will likely weigh the drugs promising efficacy, however, against this adverse event by requiring Novartis to develop a RiskMap protocol. With the expected loss of its blockbuster blood pressure drug Diovan in 2012 (more than $4 billion in expected 2009 sales), Novartis is looking to fingolimod to launch a successful new franchise in MS. Although injection-based interferon therapies are likely to remain the preferred choice (due to patient years of experience), discomfort with having to take injections daily or weekly will ensure a step on the treatment paradigm for oral drugs. And, in a market that had global sales of more than $6 billion last year - expected to exceed $9 billion by 2015 - there is room for two blockbuster oral formulations. If approved, Novartis should have two years to cement fingolimod's position as a preferred oral treatment. Come 2012, the oral MS market could get more crowded, as Teva Pharmaceuticals (laquinimod), Sanofi-Aventis (teriflunomide) and Biogen-Idec (BG-12) all have oral formulations in late stage clinical development. Source: BNET UK � 2009 CBS Interactive Inc. (07/12/09)

UK MS Society medical advisors 'unconvinced' by Zamboni's CCSVI theory

Sat, 05 Dec 2009 07:07:00 EST

Medical advisors to the UK MS Society have raised doubts about a theory put forward by Italian doctor Paulo Zamboni, who this week proposed that a vein disorder is the cause of multiple sclerosis (MS). In a statement, the experts have found fault with the theory that MS is caused by blockages in veins that drain the brain and suggest that people with MS are unlikely to benefit by any treatments developed to treat what Dr Zamboni called chronic cerebrospinal venous insufficiency (CCSVI). This week, results have been published of Dr Paulo Zamboni's work investigating whether CCSVI plays a role in multiple sclerosis (MS). The authors admit, however, that the recent paper published in the Journal of Vascular Surgery, A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency, has significant drawbacks. Last week, early news of Dr Zamboni's novel theory sparked international interest and has led to scientists at the University of Buffalo in New York to test his theory by recruiting for a large study. Research Communications Officer at the MS Society, Dr Susan Kohlhaas, said: "Several medical advisers to the MS Society have read through the papers published by Dr Zamboni, and have heard him lecture on the subject. "They are not convinced by the evidence that blockages to draining veins from the brain are specific to people with MS, or that this explains the cause of MS at any stage of the condition." Dr Zamboni's most recently published work examined CCSVI in 65 people and suggested that 50 per cent of people with relapsing remitting MS were relapse-free for 18 months. Among the control group of MS patients who did not undergo the procedure, Zamboni found that only 27 per cent went 18 months without a relapse. There was no published benefit for people with progressive forms of the condition. Participants with relapsing remitting MS, however, were allowed to continue receiving their usual form of treatment, so it is inconclusive whether any reduction in relapse rate was due to the CCSVI procedure. Importantly, the result of the procedure was measured using different MRI scanning machines and at different times, meaning the data is inconsistent and not a useful measure. Professor Alastair Compston, Head of the Department of Clinical Neurosciences at the University of Cambridge and winner of the 2007 Charcot Award for a lifetime achievement in MS research, is one of the MS Society's six medical advisors. He said: "The treatment for CCSVI is not available for patients with multiple sclerosis in the United Kingdom because there is no convincing evidence to suggest that it is safe or beneficial to people with MS. "People with MS are unlikely to benefit from treatments that dilate blood vessels." Source: MS Society (UK) � 2009 Multiple Sclerosis Society (05/12/09)

New source discovered for the generation of nerve cells in the brain

Thu, 03 Dec 2009 04:40:00 EST

The research group of Professor Magdalena Gotz of Helmholtz Zentrum Munchen and Ludwig-Maximilians-Universitat (LMU) Munich has made a significant advance in understanding regeneration processes in the brain. The researchers discovered progenitor cells which can form new glutamatergic neurons following injury to the cerebral cortex. Particularly in Alzheimer's disease, nerve cell degeneration plays a crucial role. In the future, new therapeutic options may possibly be derived from steering the generation and/or migration mechanism. These findings have been published in the current issue of the renowned journal Nature Neuroscience. Until only a few years ago, neurogenesis - the process of nerve cell development - was considered to be impossible in the adult brain. The textbooks asserted that dead nerve cells could not be replaced. Then researchers discovered regions in the forebrain in humans in which new nerve cells can be generated throughout life. These so-called GABAergic cells use gamma-aminobutyric acid (GABA), a neurotransmitter of the central nervous system. A research team of scientists led by Magdalena G�tz, director of the Institute of Stem Cell Research at Helmholtz Zentrum M�nchen and chair of the Department of Physiological Genomics of LMU, has now taken a closer look at this brain region in the mouse model. Their findings: Even in the forebrain, there are other nerve cells that are regularly generated - the so-called glutamatergic nerve cells, which use glutamate as neurotransmitter. The stem cell researchers could prove this by means of a specific transcription factor: Tbr2 is only present in progenitor cells of glutamatergic nerve cells. The newly generated nerve cells in the adult organism are located in the olfactory bulb, the region of the brain involved in the sense of smell. Nerve cells that use glutamate as a neurotransmitter are also responsible for memory - storing and retrieving information. In Alzheimer dementia, alterations in the signal transduction pathways of these special cells play a significant role. Magdalena G�tz explained the reason why this finding is so important: "Neural progenitor cells can generate these newly discovered glutamatergic nerve cells for the neighboring cerebral cortex - for example after brain injury." The research group was able to demonstrate this on the mouse model: There the cells migrated into the damaged neighboring cerebrum tissue and generated mature neurons. Accordingly, progenitor cells could then replace degenerate nerve cells. "Now it will be interesting to find out whether this process also takes place in humans, particularly in Alzheimer's patients," said Magdalena G�tz, "and also whether the process can be kept under control to avoid massive cell death." One therapeutic approach would then be to attempt to stimulate the body's own replacement mechanism. Further Information Original Publication: Monika S Brill, Jovica Ninkovic, Eleanor Winpenny, Rebecca D Hodge, Ilknur Ozen, Roderick Yang, Alexandra Lepier, Sergio Gasc�n, Ferenc Erdelyi, Gabor Szabo, Carlos Parras, Francois Guillemot, Michael Frotscher, Benedikt Berninger, Robert F Hevner, Olivier Raineteau & Magdalena G�tz: Nature Neuroscience, Volume 12 No 11 pp1351-1474 (doi:10.1038/nn.2416) Source: Medical News Today � 2009 MediLexicon International Ltd (03/12/09)

Cannabis shows promise for reducing multiple sclerosis patients' symptoms

Thu, 03 Dec 2009 02:44:00 EST

Doses of cannabis might help multiple sclerosis (MS) patients subdue their body spasms and move about more easily, according to a new review of recent studies. However, the authors of the paper note, the patients' apparent relief could also be a matter of perception. After reviewing six trials that tested the effects of tetrahydrocannabinol (THC) and cannabidiol (CBD) extracts on muscle spasms in a total of 481 MS patients, the authors found "evidence that combined THC and CBD extracts may provide therapeutic benefit." In five of the six double-blind, randomized, placebo-controlled trials the researchers analyzed, cannabis-taking patients reported decreases in their spasms. "The subjective experience of symptom reduction was generally found to be significant," wrote the authors, based at the Global Neuroscience Initiative Foundation in Los Angeles. However, the authors conceded, "participants of both active and placebo trials may not be entirely blind to their treatment status, and this may affect subjective analysis." So despite the promising patient reports, MS patients might not get a green light for this treatment just yet. "Objective measures of spasticity failed to provide significant changes," the authors concluded in the paper, published online Wednesday in the journal BMC Neurology. Cannabinoids have, however, been shown to offer neuro-protective benefits for MS patients by quelling inflammation through regulation of microglial cells' cytokine levels, and animal studies have revealed antispastic effects of the chemicals. One MS patient in New Jersey has been using the drug to treat his symptoms. "It definitely helps for the pain," John Ray Wilson told The Wall Street Journal on Monday. Wilson, however, is facing felony drug charges for growing pot plants because the state does not currently permit the use of medicinal marijuana. State lawmakers are close to changing that, which would make New Jersey residents�like those of more than a dozen other states�off limits to federal prosecution if they follow local medical marijuana laws (per a U.S. Deputy Attorney General announcement in October). Both the New Jersey Academy of Family Physicians and the New Jersey State Nurses Association have announced support for the bill, which outgoing Governor Jon Corzine has promised to sign if it passes, the Journal reported. The obvious intoxicating side effects of THC treatment have been a concern for both regulators and researchers. The authors of the recent paper, however, noted that a mixture of THC and CBD can limit psychotropic effects. In any case, they found that for the MS patients in the studies at least, "side effects from combined extracts of THC and CBD were generally well tolerated." Source: Scientific American � 1996-2009 Scientific American Inc. All Rights Reserved. (03/11/09)

Glial cells can cross from the central to the peripheral nervous system

Wed, 02 Dec 2009 08:51:00 EST

Glial cells, which help neurons communicate with each other, can leave the central nervous system and cross into the peripheral nervous system to compensate for missing cells, according to new research in the Dec. 2 issue of The Journal of Neuroscience. The animal study contributes to researchers' basic understanding of how the two nervous systems develop and are maintained, which is essential for the effective treatment of diseases such as multiple sclerosis. The nervous system is divided into the central nervous system (the brain and spinal cord) and the peripheral nervous system (sensory organs, muscles, and glands). A major difference between the systems is that each has its own type of glial cells. In a healthy body, glial cells are tightly segregated and aren't known to travel between the two systems. The peripheral nervous system also regenerates more than the central nervous system, due in part to its glial cells -- a characteristic that, if better understood, might be used to improve the regenerative capabilities of the central nervous system. Glial cells serve nerve cells by insulating them with layers of fats and proteins called myelin. Myelin coatings are necessary for nerve signals to be transmitted normally; when the sheaths are lost, disorders involving impairment in sensation, movement and cognition such as multiple sclerosis or amyotrophic lateral sclerosis develop. Glial cells named oligodendrocytes produce myelin around nerves of the central nervous system, while those named Schwann cells make myelin that insulates peripheral nerves. This study shows that in the absence of Schwann cells, oligodendrocytes migrate from the central nervous system along motor nerves and form myelin on peripheral nerves, indicating that glial cell movement across the border is controlled by a self-policing mechanism. "Past studies have hinted that Schwann cells can cross into the central nervous system after peripheral nerves near the border are damaged, or after central nerves lose their myelin sheath," said Bruce Appel, PhD, of the University of Colorado Denver Anschutz Medical Campus, one of the study's authors. "However, migration across the border has never been observed directly, nor was there any evidence that oligodendrocytes can move in the opposite direction." The authors used time-lapse video of mutant zebrafish to study the glial cell movement. Movies of translucent live zebrafish that lacked Schwann cells showed that oligodendrocytes left the central nervous system to wrap peripheral nerves with myelin -- effectively attempting to compensate for the missing Schwann cells. "This new observation is not only relevant to normal nerve function, but also to potential causes of disease in the peripheral nervous system. We're still unsure as to exactly how foreign glial cells interact with the other system. Do they help heal or do they act as a toxin?" said Bruce Trapp, PhD, at the Cleveland Clinic, who is unaffiliated with the study. "Knowing the mechanisms that anatomically restrict peripheral and central nervous system glia could help develop therapies that treat or prevent certain nervous system diseases." Appel and his colleagues said that future investigations are needed to determine how different glial cells communicate to restrict their movements between nervous systems, and whether oligodendrocyte myelin can fully substitute for Schwann cell myelin on motor nerves. The research was supported by the National Institute of Neurological Disorders and Stroke and a zebrafish initiative funded by the Vanderbilt University Academic Venture Capital Fund. Source: ScienceDaily � 1995-2009 ScienceDaily LLC (02/12/09)

Department of Health Multiple Sclerosis disease modifying drug risk sharing scheme failing people with MS

Wed, 02 Dec 2009 06:50:00 EST

In February 2002, after a period of postcode prescribing and an assessment by the National Institute of Clinical Excellence, the Department of Health (DH) announced the MS Risk-sharing Scheme, issuing Health Service Circular 2002/004. The Risk-sharing Scheme (RSS) is the mechanism that ensures the disease modifying drug therapies, beta interferon and glatiramer acetate, are available on the NHS. It also specifies the research element to assess the cost effectiveness of the drugs. The main objective of the Risk-sharing Scheme has always been to help people with MS. The Scheme is a unique initiative led by the Department of Health in conjunction with the Association of British Neurologists, the pharmaceutical industry, the MS Trust and the MS Society to give access to disease modifying drugs through the NHS. It has acted as the catalyst for the greatest improvement in MS services ever, and has thus brought tangible benefits to all people with MS across the UK. The scheme has: ■Initiated the development of a UK-wide network of over 70 MS specialist treatment centres which have improved the care and support available to all 100,000 people with MS across the UK. ■Provided around 12,000 people with relapsing-remitting MS and in some cases with secondary progressive MS, access to the drug therapy they require. ■Provided funding to increase the number of MS specialist nurses in the UK to help support all people with MS. This innovative Scheme was the first of its kind and has led to subsequent schemes being developed to give access to drugs in other disease areas. The aim of the study was to observe the effects of these drugs (over a ten-year-period) and if the four drugs in question failed to perform as promised then the manufacturers would share the risk of any potential negative outcomes by subsidising their future cost to the NHS. The scheme promised to make these drugs available to all those with MS who fitted the study criteria. Seven years into the scheme; the first two year analysis has finally been published in the British Medical Journal online. It highlights a series of methodological difficulties with the scheme, which if not addressed will result in its failure. The partners and in particular the Scientific Advisory Group have struggled with many of the complexities of modelling a long-term condition like multiple sclerosis but progress is being made as mentioned in the paper. Source: Department Oh Health, MS Trust, MS Society (02/12/09)

Long awaited results for pilot CCSVI and Multiple Sclerosis trial published

Wed, 02 Dec 2009 05:11:00 EST

A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency Objective Chronic cerebrospinal venous insufficiency (CCSVI) is characterized by combined stenoses of the principal pathways of extracranial venous drainage, including the internal jugular veins (IJVs) and the azygous (AZY) vein, with development of collateral circles and insufficient drainage shown by increased mean transit time in cerebral magnetic resonance (MR) perfusion studies. CCSVI is strongly associated with multiple sclerosis (MS). This study evaluated the safety of CCSVI endovascular treatment and its influence on the clinical outcome of the associated MS. Methods Sixty-five consecutive patients with CCSVI, subdivided by MS clinical course into 35 with relapsing-remitting (RR), 20 with secondary progressive (SP), and 10 with primary progressive (PP) MS, underwent percutaneous transluminal angioplasty (PTA). Mean follow-up was 18 months. Vascular outcome measures were postoperative complications, venous pressure, and patency rate. Neurologic outcome measures were cognitive and motor function assessment, rate of MS relapse, rate of MR active positive-enhanced gadolinium MS lesions (Gad+), and quality of life (QOL) MS questionnaire. Results Outpatient endovascular treatment of CCSVI was feasible, with a minor and negligible complication rate. Postoperative venous pressure was significantly lower in the IJVs and AZY (P < .001). The risk of restenosis was higher in the IJVs compared with the AZY (patency rate: IJV, 53%; AZY, 96%; odds ratio, 16; 95% confidence interval, 3.5-72.5; P < .0001). CCSVI endovascular treatment significantly improved MS clinical outcome measures, especially in the RR group: the rate of relapse-free patients changed from 27% to 50% postoperatively (P < .001) and of MR Gad+ lesions from 50% to 12% (P < .0001). The Multiple Sclerosis Functional Composite at 1 year improved significantly in RR patients (P < .008) but not in PP or SP. Physical QOL improved significantly in RR (P < .01) and in PP patients (P < .03), with a positive trend in SP (P < .08). Mental QOL showed significant improvement in RR (P < .003) and in PP (P < .01), but not in SP. Conclusions PTA of venous strictures in patients with CCSVI is safe, and especially in patients with RR, the clinical course positively influenced clinical and QOL parameters of the associated MS compared with the preoperative assessment. Restenosis rates are elevated in the IJVs but very promising in the AZY, suggesting the need to improve endovascular techniques in the former. The results of this pilot study warrant a subsequent randomized control study. This work was presented at the Thirty-first Charing Cross Symposium, London, United Kingdom, Apr 3-7, 2009. Paolo Zamboni, MDa, Roberto Galeotti, MDa, Erica Menegatti, RVTa, Anna Maria Malagoni, MDa, Sergio Gianesini, MDa, Ilaria Bartolomei, MDb, Francesco Mascoli, MDa, Fabrizio Salvi, MDb a Vascular Diseases Center, University of Ferrara, Ferrara, Italy b Department of Neurology, Bellaria Hospital, Bologna, Italy Source: Journal Of Vascular Surgery � 2009 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.(02/12/09)

Betaferon� approved in China for treatment of Multiple Sclerosis

Tue, 01 Dec 2009 08:46:00 EST

Bayer Schering Pharma AG announced that the Chinese State Food and Drug Administration (SFDA) has approved Betaferon� (interferon beta-1b) therapy for patients with relapsing-remitting multiple sclerosis (MS). Bayer plans to launch Betaferon in China by mid 2010. Betaferon is available in more than 100 countries around the world. �This approval is good news for MS patients in China, allowing them access to Betaferon, that has been demonstrated to modify the course of MS,� said Habib Dable, Global Head, Neurology/Ophthalmology of Bayer Schering Pharma AG. "The approval of Betaferon in China underscores Bayer�s ongoing commitment to address the unmet medical needs of people around the world. With the foundation of a research and development center in Beijing in February 2009, Bayer has strengthened its engagement in the Region. In the upcoming five years, a total of 100 million Euro is planned to be invested in a center for clinical research in Beijing." The approval is based on established efficacy and safety data from pivotal Betaferon clinical trials, along with findings from a single-arm study designed to demonstrate the efficacy and safety of Betaferon among Chinese patients with relapsing-remitting MS. During the multi-center six-month study, Betaferon significantly decreased the number of newly active lesions on MRI in Chinese patients. The data in MS patients from China is comparable with data from Betaferon studies in different patient populations and with Bayer�s post-marketing experience. About the Betaferon study in China In the multicenter single-arm open label study, 39 patients were enrolled into a three-month pre-treatment phase followed by a six-month treatment phase. The primary efficacy endpoint was the number of newly active lesions during six months on therapy. Newly active lesions were defined as new T1 Gd-enhancing lesions and non-enhancing T1 lesions appearing new (or enlarged) on T2-weighted scans at months three and six (cumulative six-month number divided by two), compared to the number of newly active lesions during a three-month pre-treatment period. In the treatment period, significant decreases were observed for the primary endpoint. The mean number of newly active lesions in the pretreatment group was 4.77, vs. the 1.55 in the treatment group (p<0.0001). Adverse events (AEs) were usually self-limiting and mild or moderate. The most frequent AEs were flu-like-symptoms, injection site reactions and hepatic function abnormality. None of the patients discontinued treatment because of AEs or laboratory toxicity. Source: Bayer Schering Pharma AG (01/12/09)

New tool in fight against autoimmune diseases, blood cancers

Tue, 01 Dec 2009 02:27:00 EST

A study led by a Scripps Research Institute scientist describes a new, highly pragmatic approach to the identification of molecules that prevent a specific type of immune cells from attacking their host. The findings add a powerful new tool to the ongoing search for potential treatments for autoimmune diseases, such as multiple sclerosis (MS), as well as blood cancers, such as myeloid leukemia. The study by Thomas Kodadek, a professor in the Chemistry and Cancer Biology Departments at Scripps Florida, and colleagues was published in the journal Chemistry & Biology. In the new study, Kodadek and his colleagues used samples from an animal model of multiple sclerosis to screen for T cells -- a type of white blood cell that plays a central role in the immune system -- with a heightened presence in the disease. The screen also identified molecules that interfere with these T cells' "autoreactivity," in other words, their attack on the body itself rather than a foreign invader such as virus or bacteria. "Our technique simultaneously uncovers and isolates autoreactive T cells as well as inhibitors to them," Kodadek said. "It's a double whammy. At the heart of this is a comparative screening process of normal T cells versus disease-causing T cells. While the process is technically complicated and difficult, the thinking behind it is not. We wanted to simplify the process of identifying compounds that could inhibit autoreactive T cells with exceptional specificity, and we succeeded." The scientists used a model of MS, an autoimmune inflammatory disease affecting the brain and spinal cord, for the study. In MS, the immune system attacks the myelin sheath covering and protecting nerve cells, leading to a variety of symptoms depending on which part of the nervous system is affected. Common symptoms of the condition include fatigue; numbness; walking, balance, and coordination problems; bladder and bowel dysfunction; vision problems; dizziness and vertigo; sexual dysfunction; pain; cognitive problems; emotional changes; and spasticity. Simplifying the Process In setting up the new method to shed light on such autoimmune diseases and other disorders, Kodadek and his colleagues created a large collection of peptoids -- molecules related to, but more stable than, the peptides that make up proteins. By arranging thousands of peptoids on a microscope slide, the pattern of binding antibodies (a type of immune molecule) and peptoids can be visualized. By looking at samples from animal models of a known disease like MS, peptoids that bind to antibodies closely associated with that disease can be easily recognized. Better still, peptoids that bind to autoreactive T cells can be identified without knowledge of the specific antigen (molecule triggering the immune attack), providing an unbiased method with which to search for potentially useful compounds. Most autoimmune research has focused on finding the disease-causing antigens first, Kodadek said, a Quixote-like quest that has lasted more than four decades with little success to show for it. "With our process, it doesn't really matter what the antigen is," said Kodadek, a 2006 recipient of the National Institutes of Health Director's Pioneer Award, which is designed to support individual scientists of exceptional creativity. "That was really the breakthrough. We're setting up a system that recognizes T cell receptors that are very abundant in a sick animal and at low levels in a healthy animal. Why the abundance? Because that's what making them sick." Potential for Therapeutic Discovery The new process creates new potential for therapeutic discovery. Molecules that target autoreactive T cells directly, while ignoring those T cells that recognize foreign antigens, could serve as the foundation for a novel drug development program aimed at eradicating autoreactive cells without affecting the normal function of the immune system. "Almost without exception, drugs currently used to treat autoimmune conditions either inhibit something downstream of the autoimmune response itself, like inflammation, or they moderate the immune system non-selectively and that results in significant side effects," Kodadek said. However, the new study isn't the final answer, according to Kodadek. He noted that the recent study used a model of MS triggered by a single antigen. In humans, there could be two -- or two dozen -- antigens triggering an autoimmune disease such as MS. This calls for further research. The method may be more easily applied to blood cancers, though, since the disease-causing T cells have been fully characterized and there are very few of them. Source: ScienceDaily � 1995-2009 ScienceDaily LLC (01/12/09)

FDA rejects Multiple Sclerosis drug Cladribine application as 'incomplete'

Mon, 30 Nov 2009 11:10:00 EST

U.S. regulators rejected as incomplete Merck KGaA's application to sell the oral treatment multiple sclerosis. Merck, the German based drugmaker will seek a meeting with the U.S. Food and Drug Administration after the agency refused to accept its application for the medicine, cladribine, spokesman Gangolf Schrimpf said. �Our next step is to request a meeting with the FDA,� Schrimpf said in a telephone interview. �We�re not in a position to discuss the details of the FDA letter.� Merck, which is vying with Novartis AG to market the first oral MS drug, asked the FDA in September to approve cladribine. �This will certainly delay market entry, the amount of time depending on the full nature of the required actions,� DZ Bank AG analysts Elmar Kraus and Thomas Maul said in a research note today. Merck�s lead over Novartis �should now be gone.� A refusal to file indicates �important information� was missing from the application, according to regulations dated 1993 that are posted on the FDA�s Web site. Minor omissions that wouldn�t significantly delay an application shouldn�t be grounds for refusal, according to the FDA rules. Compete Unlike existing injected medicines for multiple sclerosis, the Merck drug, approved more than a decade ago to fight leukemia, is taken for a few weeks out of the year in pill form. The drug works by suppressing the immune system, blunting its attack on nerve cells. Merck�s pill could compete with Novartis�s experimental multiple sclerosis pill FTY720, which disrupts the movement of immune cells into the bloodstream. Cases of cancer in people who took cladribine during a clinical trial appear �relatively non-threatening,� and the drug is likely to be adopted gradually by patients with severe forms of multiple sclerosis, Sanford C. Bernstein Ltd. analysts concluded after data was presented at the European Committee for Treatment and Research in Multiple Sclerosis congress in Dusseldorf, Germany, in September. In January, Merck said four patients were diagnosed with cancer during a final-stage trial of cladribine. An independent monitoring board was aware of the cases but didn�t consider them a safety concern, Merck said at the time. Cancer Each of the four cancer cases in the trial affected a different organ. Patients were diagnosed with early stage cervical cancer, melanoma, ovarian cancer and pancreatic cancer. Another patient developed choriocarcinoma, a cancer of the placenta, after becoming pregnant six months after she finished the study. No malignancies were reported in the placebo group. Merck asked EU regulators to approve cladribine in July. Sales of the medicine could reach 700 million euros ($1.05 billion) a year, according to an estimate by DZ Bank. Novartis has said it would ask U.S. and European regulators to approve its MS pill at the end of this year. The Swiss drugmaker has said it aims for at least $1 billion in sales for its multiple sclerosis franchise. Source: Bloomberg � 2009 Bloomberg LP (30/11/09)

Panel of multiple sclerosis experts provides best practice treatment recommendations for Tysabri

Mon, 30 Nov 2009 10:26:00 EST

Best-practice recommendations for the selection and management of patients with multiple sclerosis (MS) who may benefit from, or are receiving treatment with Tysabri� (natalizumab) were published today in a supplement to the medical journal Multiple Sclerosis. The panel provided recommendations focusing on appropriate patient selection and patient management. The recommendations, which recognize the significant efficacy of Tysabri and the need to adequately treat patients who exhibit continued disease activity, are based on U.S. prescribing information and the panel's vast clinical experience in treating MS patients with Tysabri. Recommendations not only take into account the need to adequately treat patients who exhibit continued disease activity, but also the need to weigh the treatment's benefit with potential risks. "These best-practice approaches have been developed to ensure appropriate use of this highly-effective therapy, especially with MS patients who present with continued disease activity," said Patricia K. Coyle, MD, professor and acting chair, department of neurology, Stony Brook University Medical Center and, director, Stony Brook MS Comprehensive Care Center, Stony Brook, New York. "The benefits of Tysabri are evident in that it can significantly reduce relapse rates, improve cognitive and physical disability and provide freedom from disease activity for many patients, when measured by clinical and radiological measures." One of the expert panel's recommendations encourages earlier and more rapid transition from first-line treatment to Tysabri. The recommendations also seek to lower the threshold with physicians for treating unacceptable disease activity seen in their patients. According to the panel, factors such as the nature and frequency of relapses, the location of new or unresolved MRI lesions, MRI activity in the spinal cord, rapid or persistent changes in physical disability and functional deficits in cognition should be evaluated and weighed when determining the appropriate patients to treat with Tysabri. The panel developing the recommendations, which was selected by Biogen Idec, included U.S. academic and community neurologists who, combined, have approximately 2,000 patient-years experience with TYSABRI. The panel members were: Dr. Coyle; John F. Foley, MD, director, Rocky Mountain MS Clinic, Rocky Mountain Neurological Associates; Edward Fox, MD, director, MS Clinic of Central Texas, and clinical assistant professor, University of Texas Medical Branch; Douglas R. Jeffery, MD, PhD, associate professor, department of neurology, Wake Forest University Baptist Medical Center; Frederick E. Munschauer III, MD, professor and chairman, department of neurology, State University of New York at Buffalo, and chief, The Jacobs Neurological Institute; and Carlo Tornatore, MD, associate professor, department of neurology, and director, Multiple Sclerosis Center, Georgetown University Medical Center. The paper entitled "Best Practice Recommendations for the Selection and Management of Patients with MS Receiving Natalizumab Therapy" is one of four articles that are part of a supplement being published in the journal Multiple Sclerosis. The other papers are "Introduction to Best Practice Recommendations for the Selection and Management of Patients with MS on Natalizumab," "Clinical Efficacy and Benefit of Natalizumab" and "Clinical Vigilance for PML in the Context of Natalizumab." The supplement was funded by Biogen Idec and Elan Corporation, plc. Source: Eureka Alert! (30/11/09)

Anomalous venous blood flow and iron deposition in multiple sclerosis

Mon, 30 Nov 2009 05:59:00 EST

Multiple sclerosis (MS) is primarily an autoimmune disorder of unknown origin. This review focuses iron overload and oxidative stress as surrounding cause that leads to immunomodulation in chronic MS. Iron overload has been demonstrated in MS lesions, as a feature common with other neurodegenerative disorders. However, the recent description of chronic cerebrospinal venous insufficiency (CCSVI) associated to MS, with significant anomalies in cerebral venous outflow hemodynamics, permit to propose a parallel with chronic venous disorders (CVDs) in the mechanism of iron deposition. Abnormal cerebral venous reflux is peculiar to MS, and was not found in a miscellaneous of patients affected by other neurodegenerative disorders characterized by iron stores, such as Parkinson's, Alzheimer's, amyotrophic lateral sclerosis. Several recently published studies support the hypothesis that MS progresses along the venous vasculature. The peculiarity of CCSVI-related cerebral venous blood flow disturbances, together with the histology of the perivenous spaces and recent findings from advanced magnetic resonance imaging techniques, support the hypothesis that iron deposits in MS are a consequence of altered cerebral venous return and chronic insufficient venous drainage. Full Paper - http://www.nature.com/jcbfm/journal/v29/n12/full/jcbfm2009180a.html Ajay Vikram Singh1 and Paolo Zamboni2 1Department of Physics, European School of Molecular Medicine (SEMM), IFOM-IEO Campus, Centro Interdisciplinare Materiali e Interfacce Nanostrutturati (CIMAINA), University of Milan, Milan, Italy 2Vascular Diseases Center, University of Ferrara, Ferrara, Italy Source: Journal of Cerebral Blood Flow & Metabolism (2009) 29, 1867�1878; doi:10.1038/jcbfm.2009.180 (30/11/09)

Early protein processes crucial to formation and layering of myelin membrane

Fri, 27 Nov 2009 03:57:00 EST

New findings from an international team of researchers probing the nerve-insulating myelin sheath were bolstered by the work of Boston College biologists, who used x-rays to uncover how mutations affect the structure of myelin, a focal point of research in multiple sclerosis and other neurological disorders. The findings were central to the group's broader conclusion that a set of protein processes required in the early-stage conversion of glucose into fatty acids are critical to the proper formation and layering of myelin membrane, the researchers report in the Proceedings of the National Academy of Sciences. Boston College Professor of Biology Daniel Kirschner, Senior Research Associate Hideyo Inouye, graduate student Adrienne Luoma, and undergraduate Michelle Crowther partnered with Dutch, Italian, Swiss and Japanese scientists. The research group looked at the composition of myelin lipids for clues about their role in myelin structure and stability, Kirschner said. Myelin sheaths surround the axons of neurons and are considered critical to the proper functioning of the nervous system. "Myelin is a stack of membranes providing insulation to the axon and with that insulation comes rapid nerve conduction," said Kirschner. "If myelin becomes defective, the membranous insulator becomes leaky and the nerve doesn't conduct as well. If myelin is totally missing along part of an axon, the nerve conduction is blocked." Using x-ray diffraction, Kirschner's group captured a view of the dynamic membrane assembly in whole nerve samples taken from mice engineered to mimic myelinic diseases. Compared to other microscopy techniques used in the study of myelinated tissue, x-ray diffraction delivers clearer, cleaner and quicker results about the structural integrity of internodal myelin, Kirschner said. "We were able to tell that the packing of the membranes was abnormal, which could affect the electrophysical properties of myelin," said Kirschner. "We also saw that the packing of the lipids in the myelin lipid bilayers was more disordered in samples from the transgenic mice used here." Other types of microscopy introduce chemical modifications to the tissue under study. These agents and the time involved in preparing and analyzing such samples can alter the molecular structure and mask the dynamic interactions of myelin. X-ray diffraction requires no chemical treatments and can be completed in about an hour, Kirschner said. "The advantages of x-ray diffraction are that we can examine and analyze whole pieces of tissue and give information about the effect of the mutation on the native structure of the myelin as well as on its stability," said Kirschner. The researchers have been focusing on genetically modified mice for approximately four years as part of research into the role of myelin degeneration in a range of diseases of the central and peripheral nervous systems. Kirschner says his team is also exploring use of the technique in animal models of spinal cord injury and repair. Source: Medical News Today � 2009 MediLexicon International Ltd (27/11/09)

Multiple sclerosis 'blood blockage theory' tested

Fri, 27 Nov 2009 02:08:00 EST

US scientists are testing a radical new theory that multiple sclerosis (MS) is caused by blockages in the veins that drain the brain. The University of Buffalo team were intrigued by the work of Italian researcher Dr Paolo Zamboni who claims 90% of MS is caused by narrowed veins. He says the restricted drainage, visible on scans, injures the brain leading to MS. He has already widened the blockages in a handful of patients. The US team want to replicate his earlier work before treating patients. Experts welcomed the research saying it was important to confirm the basic science before evaluating any therapy. MS is a long-term inflammatory condition of the central nervous system which affects the transfer of messages from the nervous system to the rest of the body. The Buffalo team, led by Dr Robert Zivadinov, plan to recruit 1,100 patients with MS and 600 other volunteers as controls who are either healthy or have neurological diseases other than MS. Using Doppler ultrasound, they will scan the patients to see if they can find any blockages within the veins of the neck and brain. If they can prove Dr Zamboni's theory of " chronic cerebrospinal venous insufficiency", they say it will change our understanding of MS. Rewriting science Margaret Paroski, who is chief medical officer at Kaleida Health, where the Buffalo researchers are based, said the work could overturn prevailing wisdom that the damage in MS is predominantly the result of abnormal immune responses. "When I was in medical school, we thought peptic ulcer disease was due to stress. We now know that 80% of cases are due to a bacterial infection. "Dr Zivadinov's work may lead to a whole different way of thinking about MS." Dr Zamboni, of the University of Ferrara, believes the blockages are the cause rather than the consequence of MS and that they allow iron from the blood to leak into the brain tissue, where it causes damage. He has performed procedures similar to angioplasty to unblock the veins and get the blood flowing normally again. He claims this "liberation procedure" can alleviate many of the symptoms of MS and is due to publish his findings in the Journal of Vascular Surgery. In an interview with CTV News in Canada he said: "I found the evidence of narrowing - narrowing of the veins just in MS patients. "I'm fully convinced that this is very, very important for people." Early days Kevin Lipp, an MS patient from the US, has been symptom-free since being treated by Dr Zamboni. He said: "It's only been 10 months. If nothing happens in the next two to three years, we'll know it's working." The BBC has heard anecdotally of other surgeons in Europe testing out the same treatment. The MS Society said more research was needed to see if this was an avenue that should be explored further. "This is not something patients can expect as a treatment now. This is experimental work and is being tested. We need to know more about its safety and effectiveness." Helen Yates, of the MS Resource Centre (MSRC), said: "There is no doubt that this area warrants a great deal more study. "This could represent a completely novel approach to MS research which, if proven to be relevant, could be a "sea change" in the understanding of the mechanisms involved in the condition." Source: BBC News � British Broadcasting Corporation 2009 (27/11/09)

Canadian Multiple Sclerosis specialist questions validity of CCSVI theory but his motives are questioned by audience

Thu, 26 Nov 2009 02:48:00 EST

Research head at The Ottawa Hospital questions validity of clogged veins theory during education session. The �liberation procedure,� a controversial new surgical procedure that appears to cure multiple sclerosis, is based on circumstantial evidence and MS sufferers should not rush into getting it. That was the message delivered by Dr. Mark Freedman, director of the MS research unit at The Ottawa Hospital, during an education session hosted by the MS Society of Ottawa on Tuesday night. For many in the audience, his words dashed much of their newfound hope. One of a series of education events regularly presented by the society, this meeting attracted throngs of MS patients and their loved ones, all curious about the new theory proposed by Italian researcher Dr. Paolo Zamboni. A vascular surgeon by training, Zamboni believes MS is not an autoimmune condition, as widely believed, but rather a vascular disease that can be cured with surgery. Zamboni�s theory is that MS is caused by clogged veins, a condition he calls �chronic cerebrospinal venous insufficiency� (CCSVI). Zamboni first performed the angioplasty-type surgery on his wife, who suffered from MS, and her symptoms disappeared. He then tested it on a group of 65 patients with remarkable results: 73 per cent had no symptoms two years after the surgery. However, Freedman, like many neurologists, is skeptical. During his presentation, Freedman said he confronted Zamboni at a recent meeting in Lisbon. �He was there presenting some of his data and had a hard time answering any of the questions from the MS guys,� Freedman said. Among their concerns was Zamboni�s claim that the clogged veins are present at birth, yet no studies had been done on children. Zamboni had not done animal studies, either. �I said, �Why don�t you tie off a few of the blood vessels in animals and see if they develop MS?� His answer was, �I�m not a mouse researcher�,� Freedman said. �If his observation stands up to other people being able to reproduce it,� Freedman said, �I think we�re going to have something of interest to chase, but we need to have the supporting evidence before we start reaming out blood vessels and pretending that this is going to cure the disease.� Still, the fact that most of Freedman�s presentation was devoted to explaining the new drugs that are being developed to treat MS did not satisfy many members of the audience on Tuesday night. �The problem I have is that you take Dr. Zamboni�s work very lightly, and, quite frankly, you haven�t done any better,� Mike Sastre said during the question-and-answer session. His wife, Linda Hume-Sastre, has lived with MS for almost seven years. �All I want to say is give the man a chance, give the people here a chance who haven�t been helped very much by what you�re promoting,� Sastre said. �If they get better using something very simple, you lose a lot of research money, and so does the MS Society.� Zamboni�s research has given hope to MS patients such as Dayle Baich, who uses a walker to get around. �This I would do,� Baich said. �It�s a very simple surgery, compared to two years of chemotherapy. In three years, I have gone from being normal to now. So where am I going to be in two or three more years? I don�t have the time. Neither do most of the people here.� The MS Society of Canada has issued an invitation for research operating grant proposals on CCSVI related to multiple sclerosis from qualified investigators based in Canadian institutions. The competition opens Dec. 9. The deadline for applications is Jan. 22. Source: The Ottawa Citizen � The Ottawa Citizen (26/11/09)

High unexpressed anger in Multiple Sclerosis patients linked to nervous system damage, not disease severity

Tue, 24 Nov 2009 12:03:00 EST

People with multiple sclerosis (MS) feel more than twice as much withheld anger as the general population and this could have an adverse effect on their relationships and health, according to a study published in the December issue of the European Journal of Neurology. Italian researchers assessed 195 patients with MS, using a range of scales that measure anger, depression and anxiety, and then compared them with the general population. They were surprised by the results, which showed that while patients experienced almost twice the normal level of withheld anger and exerted low levels of control on their anger, their expressed anger levels were similar to the general population. This, together with the fact that the elevated withheld anger levels were not related to the severity of the patients' MS, suggests that these inconsistent changes were caused by nervous system damage, rather than an emotional reaction to the stress of the disease. "We believe that the higher levels of withheld anger shown by the study subjects is due to demyelination, loss of the substance in the white matter that insulates the nerve endings and helps people receive and interpret messages from the brain" explains lead researcher Dr Ugo Nocentini from the IRCCS S Lucia Foundation in Rome. "The way we process anger is controlled by complex interconnections between the subcortical and cortical systems, notably the amygdale and basal ganglia and the medial prefrontal cortex. We believe that the demyelination process that causes the root symptoms of MS also disrupts the pathways that control how we deal with withheld anger." The patients who took part in the study comprised 150 with relapsing-remitting MS and 45 with progressive MS. More than two-thirds (68 per cent) were women, the average age of the participants was 40 and the average time since diagnosis was 11 years. Researchers evaluated the participants using the State Trait Anger Expression Inventory, the Chicago Multiscale Depression Inventory and the State Trait Anxiety Inventory. The researchers then looked at age and sex-matched subjects in the general population and identified the levels of anger experienced by the 25 per cent of people with the highest scores. They found that MS patients: �Were more than twice as likely to experience high levels of withheld anger, with 60 per cent of patients recording the same high levels as the top 25 per cent of the general population. �Exerted a low level of control on their anger, with just 11 per cent of patients reporting the same high levels of control compared to the top 25 per cent of the general population. �Were about the same as non MS patients when it came to expressed anger, with 30 per cent of patients reporting the same high levels as the top 25 per cent of the general population. During the study the authors also compared the anger scores against selected demographic and clinical characteristics and found they were independent of age, education, disease duration and course, disability and fatigue severity. The only notable difference was that women reported higher levels of current anxiety. "Our findings clearly show that anger characteristics in MS patients differ from those observed in the general population and the overall results surprised the research team" concludes Dr Nocentini. "For example, patients reported low levels of anger control and high levels of withheld anger, yet the scores for expressed anger were similar to those of the general population. "We would have expected greater consistency between withheld and expressed anger and higher levels of expressed anger as a consequence of low anger control." The authors conclude that damage to the fibres in the areas of the brain where anger issues are processed is the most logical explanation. They also say the findings have important implications for clinical practice. "Anger disrupts interpersonal relationships and this is particularly true for withheld anger, which might go unrecognised by other people" says Dr Nocentini. "Witheld anger has been reported to be associated with physical problems, in particular high blood pressure and vascular disorders, and may have a negative effect on the general health of MS patients. "Because withheld anger has no, or few, overt manifestations, and is unlikely to be recognised by clinicians or reported by patients, it is important that MS patients are asked if they experience abnormal anger." Source: Science Daily � 1995-2009 ScienceDaily LLC (24/11/09)

Factors from common human bacteria may trigger multiple sclerosis

Tue, 24 Nov 2009 05:31:00 EST

Current research suggests that a common oral bacterium may exacerbate autoimmune disease. The related report by Nichols et al, "Unique Lipids from a Common Human Bacterium Represent a New Class of TLR2 Ligands Capable of Enhancing Autoimmunity," appears in the December 2009 issue of The American Journal of Pathology. Multiple sclerosis (MS), a disease where the immune system attacks the brain and spinal cord, affects nearly 1 in 700 people in the United States. Patients with multiple sclerosis have a variety of neurological symptoms, including muscle weakness, difficulty in moving, and difficulty in speech. Porphyromas gingivalis, a common oral bacterium in humans, produces a unique type of lipid, phosphorylated dihydroceramides (DHCs), which enhance inflammatory responses. These lipids are also likely produced by bacteria found in other parts of the body including the gastrointestinal tract. To determine if these lipids accentuate immune-mediated damage in autoimmune disease, researchers led by Robert B. Clark and Frank C. Nichols of the University of Connecticut Health Center administered phosphorylated DHCs in a mouse model of MS. The severity of disease was significantly enhanced by the addition of these lipids in a manner that was dependent on activation of the immune system. These data suggest that phosphorylated DHCs from bacteria commonly found in humans may trigger or increase the severity of autoimmune diseases such as multiple sclerosis. The authors state that "while it is clear that the immune system in most individuals has the potential to attack self-tissues, the "tipping" factors that initiate and propagate autoimmune diseases such as multiple sclerosis in only a subset of individuals remain unknown. Overall, [their] results represent the first description that phosphorylated DHCs derived from common human bacteria are capable of enhancing autoimmune disease." Thus, these lipids may function as "tipping" factors, playing a previously unrecognized role in initiating or exacerbating human autoimmune diseases. In future studies, Dr. Clark and colleagues plan to characterize the effects of phosphorylated DHCs on specific cells of the immune system and to identify how and where these lipids are deposited in tissues throughout the body. In addition to the role of these lipids in triggering and worsening MS, the authors believe that phosphorylated DHCs may have the potential to serve both as new markers of MS disease activity and as new targets for therapeutic intervention. Source: Scinece Codex (24/11/09)

MS Society of Canada announces request for research operating grants related to CCSVI and MS

Tue, 24 Nov 2009 02:16:00 EST

The Multiple Sclerosis Society of Canada announced it will request research operating grants related to chronic cerebrospinal venous insufficiency (CCSVI) and MS. A recent study released by Dr. Paulo Zamboni, University of Ferrara, Italy, describes CCSVI as a disruption of blood flow in which the venous system is not able to efficiently remove blood from the central nervous system resulting in increased pressure in the veins of the brain and spinal cord which in turn results in damage to these areas. �These early results are encouraging and show that this warrants more study,� said Yves Savoie, MS Society President and CEO. �This is truly a new avenue to explore in MS research, and we want to be a part of furthering this investigation.� The MS Society of Canada will issue an invitation for research operating grant proposals on CCSVI related to multiple sclerosis from qualified investigators based in Canadian institutions. Proposals will be evaluated for their scientific merit and relevance to the field of MS. The competition will open on December 9, 2009, and the deadline for applications will be January 22, 2010. �There has been tremendous interest and excitement about this study from people with MS, supporters, volunteers and staff across the country. While we acknowledge that the concept of CCSVI as a cause of MS needs to be replicated and validated in larger well-designed studies, the Society looks forward to contributing to this body of work,� said Savoie. While excited about the potential of the CCSVI study, the findings are preliminary. Thus the MS Society advises that while further research is underway people follow their physician's recommendations and continue their current course of therapies. Source: Multiple Sclerosis Society of Canada (24/11/09)

Warning on cancer risk from stem cell therapy

Mon, 23 Nov 2009 04:35:00 EST

Experts fear that a Victorian man with leukaemia may be the first Australian ''infected'' with cancer after treatment at a private overseas stem cell therapy centre. Stem cell specialists and patient support groups are calling for more public education about the dangers of such services, saying they get hundreds of calls a year from people considering using them - and the numbers are rising. The companies advertise on the internet and via local information sessions, offering injections of foetal stem cells and stem cells extracted from the patient's spinal cord. They claim to treat conditions such as Alzheimer's, multiple sclerosis, diabetes, autism and spinal injury. Private, largely unregulated clinics in Asia and Europe charge tens of thousands of dollars plus travel costs. However few have published, clinical proof of their efficacy, relying instead on slick websites and individual testimonies. Advocacy groups for people targeted as possible clients will meet in Canberra today to discuss how to protect people from being emotionally and financially exploited. The stem cell treatments ranged in quality and safety but very few, if any, offered genuine hope, said Dr Kirsten Herbert, a hematologist at the Peter MacCallum Cancer Centre and clinical adviser to the Australian Stem Cell Centre (ASCC). ''One man in Queensland paid $40,000 for a treatment [at a private German clinic] and was told he needed two or three more [visits] for a treatment that I cannot imagine, even with the most blue-sky open mind, could have helped him,'' she said. ''But they will take his money and not do anything to look after him when he leaves. If we practised a treatment like that we would be disbarred.'' Dr Herbert plans next month to investigate the case of a Victorian man being treated for leukaemia, which was diagnosed after his recent return from overseas stem cell therapy. She said it was difficult to prove a link, but there was an international precedent: in February the journal PLoS Medicine reported the case of a teenage Israeli boy who developed brain tumours from experimental stem cell injections at a Russian clinic. Dr Herbert said cancer was a rare but possible side-effect of experimental stem cell therapy. ''Most stem cells grow in a culture that is exposed to proteins and hormones that encourage growth, and cancer is out-of-control growth, so these cells have a greater potential to cause cancer,'' she said. Other risks included contamination from animal products used in laboratory processing of the stem cells, which could introduce Creutzfeldt-Jakob disease. Some clinics also instructed patients to go on medication to suppress their immune systems, with potentially dangerous side-effects. ''They don't follow these patients up,'' Dr Herbert said. ''They prescribe and wave goodbye without any duty of care.'' The financial and emotional risks to patients were just as great, Dr Herbert said. ''Most likely, the treatment you are going to receive is not going to work.'' It was important not to demonise people who sought these cures, but instead to help them find the right advice. Patient advocacy groups are meeting stem cell experts in Canberra today to discuss a co-ordinated approach to public education on overseas experimental treatments. The ASCC is about to release a patient handbook to help people critically analyse stem cell treatments. It has a list of questions to ask before signing up. Source: The Age.com.au � 2009 Fairfax Digital (23/11/09)

Vitamin D - the missing link for multiple sclerosis sufferers

Sun, 22 Nov 2009 04:19:00 EST

Scientists have uncovered increasing evidence of the significance of Vitamin D in the development of multiple sclerosis. Now, Australian researchers have found that Vitamin D may actually reduce its symptoms. Professor Bruce Taylor, a principal research fellow at the Menzies Institute in Hobart, studied 145 patients in southern Tasmania and tracked their seasonal susceptibility to the disease. He looked at how Vitamin D levels influenced their risk of having an attack of MS. 'We found that the higher your Vitamin D level, the lower your chance of relapse, and for each ten nanomole [a standard measure of concentration of Vitamin D in the blood] increase in Vitamin D, you can reduce your risk of having an attack of MS by about ten per cent. Doubling your Vitamin D will reduce your risk by up to 50 per cent - a major result.' Helen Yates, the Multiple Sclerosis Resource Centre's chief executive, says: 'It has long been believed that Vitamin D has a role to play in the risk of developing MS but this new research opens up the strong possibility that this vitamin could impact on relapse rates.' The MS Society's research communications officer, Dr Susan Kohlhaas, says: 'These results are very early-stage and need to be reviewed and validated before we draw any firm conclusions.' It has been known for many years that the further you live from the Equator, the more likely you are to develop MS. For example, Malaysia has hardly any sufferers but in Scotland and Scandinavia MS is relatively common. It is believed this is due to a shortage of Vitamin D; countries far from the Equator, such as those in Northern Europe, enjoy less sunshine, the main source of Vitamin D. Research has shown that babies born in May - who developed in the womb during the Vitamin D-scarce winter months - are the most likely to get MS in later life, while those born in November are at much lower risk. Another study this year found evidence that Vitamin D deficiency during pregnancy and infancy could increase a child's risk of developing MS in later life. The researchers concluded that taking Vitamin D supplements during these times could reduce the risk, although this has yet to be proven. Source The Mail Online � 2009 Associated Newspapers Ltd (22/11/09)

Researcher's labour of love leads to breakthrough in treating Multiple Sclerosis

Sun, 22 Nov 2009 03:08:00 EST

� I am confident that this could be a revolution for the research and diagnosis of multiple sclerosis � � Dr. Paolo Zamboni Elena Ravalli was a seemingly healthy 37-year-old when she began to experience strange attacks of vertigo, numbness, temporary vision loss and crushing fatigue. They were classic signs of multiple sclerosis, a potentially debilitating neurological disease. It was 1995 and her husband, Paolo Zamboni, a professor of medicine at the University of Ferrara in Italy, set out to help. He was determined to solve the mystery of MS � an illness that strikes people in the prime of their lives but whose causes are unknown and whose effective treatments are few. What he learned in his medical detective work, scouring dusty old books and using ultra-modern imaging techniques, could well turn what we know about MS on its head: Dr. Zamboni's research suggests that MS is not, as widely believed, an autoimmune condition, but a vascular disease. More radical still, the experimental surgery he performed on his wife offers hope that MS, which afflicts 2.5 million people worldwide, can be cured and even largely prevented. �I am confident that this could be a revolution for the research and diagnosis of multiple sclerosis,� Dr. Zamboni said in an interview. Not everyone is so bullish: Skeptics warn the evidence is too scant and speculative to start rewriting medical textbooks. Even those intrigued by the theory caution that MS sufferers should not rush off to get the surgery � nicknamed the �liberation procedure� � until more research is done. U.S. and Canadian researchers are trying to test Dr. Zamboni's premise. For the Italian professor, however, the quest was both personal and professional and the results were stunning. Fighting for his wife's health, Dr. Zamboni looked for answers in the medical literature. He found repeated references, dating back a century, to excess iron as a possible cause of MS. The heavy metal can cause inflammation and cell death, hallmarks of the disease. The vascular surgeon was intrigued � coincidentally, he had been researching how iron buildup damages blood vessels in the legs, and wondered if there could be a similar problem in the blood vessels of the brain. Using ultrasound to examine the vessels leading in and out of the brain, Dr. Zamboni made a startling find: In more than 90 per cent of people with multiple sclerosis, including his spouse, the veins draining blood from the brain were malformed or blocked. In people without MS, they were not. He hypothesized that iron was damaging the blood vessels and allowing the heavy metal, along with other unwelcome cells, to cross the crucial brain-blood barrier. (The barrier keeps blood and cerebrospinal fluid separate. In MS, immune cells cross the blood-brain barrier, where they destroy myelin, a crucial sheathing on nerves.) More striking still was that, when Dr. Zamboni performed a simple operation to unclog veins and get blood flowing normally again, many of the symptoms of MS disappeared. The procedure is similar to angioplasty, in which a catheter is threaded into the groin and up into the arteries, where a balloon is inflated to clear the blockages. His wife, who had the surgery three years ago, has not had an attack since. The researcher's theory is simple: that the underlying cause of MS is a condition he has dubbed �chronic cerebrospinal venous insufficiency.� If you tackle CCSVI by repairing the drainage problems from the brain, you can successfully treat, or better still prevent, the disease. �If this is proven correct, it will be a very, very big discovery because we'll completely change the way we think about MS, and how we'll treat it,� said Bianca Weinstock-Guttman, an associate professor of neurology at the State University of New York at Buffalo. The initial studies done in Italy were small but the outcomes were dramatic. In a group of 65 patients with relapsing-remitting MS (the most common form) who underwent surgery, the number of active lesions in the brain fell sharply, to 12 per cent from 50 per cent; in the two years after surgery, 73 per cent of patients had no symptoms. Augusto Zeppi, a 40-year-old resident of the northern Italian city of Ferrara, was one of those patients. Diagnosed with MS nine years ago, he suffered severe attacks every four months that lasted weeks at a time � leaving him unable to use his arms and legs and with debilitating fatigue. �Everything I was dreaming for my future adult life, it was game over,� he said. Scans showed that his two jugular veins were blocked, 60 and 80 per cent respectively. In 2007, he was one of the first to undergo the experimental surgery to unblock the veins. He had a second operation a year later, when one of his jugular veins was blocked anew. After the procedures, Mr. Zeppi said he was reborn. �I don't remember what it's like to have MS,� he said. �It gave me a second life.� Buffalo researchers are now recruiting 1,700 adults and children from the United States and Canada. They plan to test MS sufferers and non-sufferers alike and, using ultrasound and magnetic resonance imaging, do detailed analyses of blood flow in and out of the brain and examine iron deposits. Another researcher, Mark Haacke, an adjunct professor at McMaster University in Hamilton, is urging patients to send him MRI scans of their heads and necks so he can probe the Zamboni theory further. Dr. Haacke is a world-renowned expert in imaging who has developed a method of measuring iron buildup in the brain. �Patients need to speak up and say they want something like this investigated � to see if there's credence to the theory,� he said. MS societies in Canada and the United States, however, have reacted far more cautiously to Dr. Zamboni's conclusion. �Many questions remain about how and when this phenomenon might play a role in nervous system damage seen in MS, and at the present time there is insufficient evidence to suggest that this phenomenon is the cause of MS,� said the Multiple Sclerosis Society of Canada. The U.S. society goes further, discouraging patients from getting tested or seeking surgical treatment. Rather, it continues to promote drug treatments used to alleviate symptoms, which include corticosteroids, chemotherapy agents and pain medication. Many people with multiple sclerosis, though, are impatient for results. Chatter about CCSVI is frequent in online MS support groups, and patients are scrambling to be part of the research, particularly when they hear the testimonials. Kevin Lipp, a 49-year-old resident of Buffalo, was diagnosed with MS a decade ago and has suffered increasingly severe attacks, especially in the heat. (Heat sensitivity is a common symptom of MS.) His symptoms were so bad that he was unable to work and closed his ice-cream shop. Mr. Lipp was tested and doctors discovered blockages in both his jugular and azygos veins. In January of this year, he travelled to Italy for surgery, which cleared five blockages, and he began to feel better almost immediately. �I felt good. I felt totally normal. I felt like I did years ago,� he said. He has not had an attack since. As part of the research project, Mr. Lipp's siblings have also been tested. His two sisters, both of whom have MS, have significant blockages and iron deposits, while his brother, who does not have MS, has neither iron buildup nor blocked arteries. While it has long been known that there is a genetic component to multiple sclerosis, the new theory is that it is CCSVI that is hereditary � that people are born with malformed valves and strictures in the large veins of the neck and brain. These problems lead to poor blood drainage and even reversal of blood flow direction that can cause inflammation, iron buildup and the brain lesions characteristic of multiple sclerosis. It is well-established that the symptoms of MS are caused by a breakdown of myelin, a fatty substance that coats nerve cells and plays a crucial role in transmitting messages to the central nervous system. When those messages are blurred, nerves malfunction, causing all manner of woes, including blurred eyesight, loss of sensation in the limbs and even paralysis. However, it is unclear what triggers the breakdown of myelin. There are various theories, including exposure to a virus in childhood, vitamin D deficiency, hormones � and now, buildup of iron in the brain because of poor blood flow. While he is convinced of the significance of his discovery, Dr. Zamboni recognizes that medicine is slow to accept new theories and even slower to act on them. Regardless, he can take satisfaction in knowing that the woman who inspired the quest, and perhaps a dramatic breakthrough, has benefited tremendously. Dr. Zamboni's wife, Elena, has undergone a battery of scans and neurological tests and her multiple sclerosis is, for all intents and purposes, gone. �This is probably the best prize of the research,� he said. Source: The Globe & Mail � Copyright 2009 CTVglobemedia Publishing Inc (22/11/09)

Fifty percent of MS patients avoid treatment over injectable delivery fears

Fri, 20 Nov 2009 04:02:00 EST

Around half of all multiple sclerosis (MS) patients that are eligible for treatment do not receive it and one in five of those patients that do begin therapy, delay doing so because of fear and anxiety over the treatment process, and not fear and anxiety about the disease. These observations are according to Patricia Kennedy, a nurse practitioner and consultant at Can Do Multiple Sclerosis, formerly The Heuga Center for MS, US, who presented at the 2nd Vetter Drug Management Leadership Conference in Germany. �If the injectable therapies that we have available today are good for MS, good for patients, and good for the future, why aren�t patients taking them?� questioned Kennedy. �It is important for industry to be aware of MS patients� reasons for avoiding treatment and what they go through when facing the disease,� she added. She then urged delivery-device manufacturers to consider patient behaviour and feelings when developing new devices in order to increase a patient�s chances of initiating therapy and complying with long-term treatment. According to Kennedy, healthcare professionals face a number of challenges when dealing with MS patients, with those who are eligible for therapy opting out of treatment for a number of reasons, including: lack of belief that it is needed; fear of needles; the constant reminder of the disease each time they need to inject; lack of family support; and the financial burden of treatment. �Even in those patients that do begin treatment, it�s another challenge to keep them on it,� admitted Kennedy. She also advised of the problems that US healthcare systems currently face with disposal of syringes and sharp objects; this is a particular problem in more populated regions in the US. Education of patients and their support networks is incredibly important to help with patient compliance and disease management. However, Kennedy also provided advice to industry on how new device development might help MS patients to manage and control their disease since injection-related issues are still a primary cause for patient�s fear of starting therapy and is the main reason for lack of compliance. What can industry do? �The easier we can make it for a patient to administer treatment, the more likely it is that the medication is going to be used,� explained Kennedy. �In most cases, the smaller the needle, the better. Although a 29-gauge needle might be easier to use than a 30-gauge needle, and although both are small, the patient will opt for the slimmer 30-gauge every time. Psychologically, that�s what they want,� she added. According to Kennedy, patients want titrated, prefilled syringes that are marked clearly. Not only does this avoid any issues of efficient mixing and incorrect dosing, but MS patients often have vision problems. Kennedy also emphasized the importance of travel devices, such as pens. �Patients want devices that are easy to travel with because we live in a mobile society, and if we provide the option of transporting less bulky injections devices whilst they�re away from home, patients are more likely to comply with their medication,� she advised. In general, Kennedy also believes that injection devices could help patients immensely. �Most patients like injectors; even if the needle is a 30-gauge needle, patient�s don�t want to see it. So if you can hide the injector, then that�s good. It�s psychological,� she said. Injection devices not only help overcome the psychological barrier to injections, but they are also easier to use than syringes, which is especially beneficial for those patients that suffer from tremors. In addition, they help patients to obtain a consistent depth of injection and thus reduce the number of injection-related side effects. �I also believe that needless devices would help improve patient compliance with drug therapy,� added Kenney. The bottom-line for patients, according to Kennedy, is to provide them with delivery devices that are easy to use, offer choice and flexibility, with increased comfort. �What patients really want, first of all, is control over their MS � easily-injectable systems can help with that. They want to be self-effective, they want a medication that�s easy to use because then they�re not reminded about their MS, and if they�re reminded less often then life goes on and they�re able to pursue other things. �So in the future, I would urge industry to continue to make injectable devices that are more patient-friendly. We need to work together to decrease the number of non-users; let�s raise that 50% to 75%,� she insisted. �I doubt we�ll ever make 100%, but we can lessen the impact of MS on a person�s life by giving them maximum control and letting them get on with their life. If we treat people early with the medications, we already have available to us today, and treatment is consistent and easy to administer, it gives them hope for the future,� she concluded. Source: Pharmatech.com � 2009 Advanstar Communications, Inc (20/11/09)