Sep 19, 2008
Presentations from leading MS researchers during the third day of this unprecedented gathering in Montreal, Quebec highlighted the changing landscape of MS, new insights into risk factors and progress in the search for better treatments. The Plenary session ECTRIMS Lecture by Chris Polman, MD, (Free University, The Netherlands) explored concepts related to what has been and can be learned from treating MS and its animal models, even from studies that are unsuccessful, and the opportunities for deeper understanding of the disease presented by both large-scale and small clinical studies.
Reports on Emerging Therapies
• More patients remained relapse-free and stable while taking experimental alemtuzumab (Genzyme Corporation) compared with those taking a standard interferon, supporting other beneficial measures previously reported from a Phase 2 study of the annual IV infusion, now in Phase 3 trials. Krzysztof Selmaj, MD, PhD (Klinika J Katedra Neurologii Akademii, Lodz, Poland) presented data on the Phase 2 study, which evaluated high and low doses of this immune-suppressing monoclonal antibody compared with Rebif® (interferon beta-1a, EMD Serono, Inc. and Pfizer, Inc.) in people with relapsing-remitting MS who had never taken any other disease-modifying therapies. Immune thrombocytopenic purpura, thyroid adverse events, and infections occurred more frequently in the alemtuzumab groups. (Abstract 55)
• First results from a one-year, multi-center trial of T-cell vaccination (Tovaxin, Opexa Therapeutics) were presented by Edward Fox, MD, PhD (University of Texas Medical Branch, Round Rock Texas). The placebo-controlled study involved 140 patients with relapsing-remitting MS and 10 patients who had experienced a neurological episode (CIS) that put them at possible risk for being diagnosed with MS. Those on treatment received five monthly subcutaneous injections of their own attenuated immune T cells and followed for one year. The treatment was found to be safe, but did not achieve statistical significance in the primary endpoint evaluating the cumulative number of active MRI lesions (gadolinium-enhanced) in those on active therapy versus those on placebo. Dr. Fox stated that additional evaluations of the immunological and other effects of the treatment are ongoing, with an eye toward the design of further clinical trials. (Abstract 56).
• A recent study found that one course of the IV drug Rituxan® (rituximab, Genentech and Biogen Idec) reduced disease activity and relapses for 48 weeks in people with relapsing-remitting MS. Today Robert Naismith, MD (Washington University, St. Louis, Mo.) presented results of an investigator-initiated study supported in part by the National MS Society (USA) suggesting that this drug, which depletes immune B cells, has potential for treating “breakthrough” disease activity in people still taking a standard MS therapy. Twenty-six people who were on disease-modifying therapies but showing active MRI-detected lesions received four doses of rituximab while staying on their other therapy. At the end of 24 weeks, their disability status score (EDSS) remained unchanged, but another functional measure called the MS Functional Composite (MSFC) improved over baseline. (Abstract P476). In an earlier presentation by the same group, they also reported finding, to their surprise, that rituximab not only depleted B cells, but also T cells. (Abstract 31)
• According to investigators reporting the first results from an early, uncontrolled trial of injections of mesenchymal stem cells (grown from the patients’ own bone marrow) in a small number of individuals with MS and ALS, this approach may warrant longer, controlled investigations. Dimitrios Karussis, MD, PhD (Hadassah-Hebrew University, Jerusalem) reported that 15 individuals with advanced MS and 14 with advanced ALS received intrathecal and intravenous injections of the cells. According to the report, the ALS patients remained stable for 6 months and MS patients showed improvement on disability status scores (EDSS) at 3 months and 6 months. Twenty patients experienced mild fever and transient meningeal irritation. (Abstract 57)
• Results of a small-scale safety trial of the experimental peptide therapy ATX-MS-1467 were presented by David C. Wraith, PhD (University of Bristol, UK). This compound is a “cocktail” of four peptides derived from human myelin basic protein, a major component of the myelin that is attacked in MS. The vaccine was tested in 6 people with secondary-progressive MS and was well tolerated. Lab tests also showed that it suppressed responses to MBP by immune T cells of the participants. This preliminary study was funded by Apitope Ltd. According to Dr. Wraith, the company hopes to conduct a larger clinical trial in the future. (Abstract P533)
Reports on Current Therapies
• Ralf Gold, MD (University Clinic Bochum at St. Josef Hospital, Bochum, Germany) described one of two recently reported cases of PML among individuals who had been prescribed Tysabri® (natalizumab, Biogen Idec and Elan Pharmaceuticals) as a monotherapy (not in combination with other therapies). PML (progressive multifocal leukoencephalopathy) is a viral infection of the brain that usually leads to death or severe disability. He described steps that led to the PML diagnosis and its subsequent treatment in a 52-year-old patient from Germany who had had MS for 16 years and had been taking Tysabri for 14 months. He advised doctors in the audience not to administer Tysabri if a patient is showing new signs or symptoms unless the possibility of JC virus activation has been excluded. (Abstract 84)
• The latest safety data on Tysabri (natalizumab, Biogen Idec and Elan Pharmaceuticals), also presented at the Congress, revealed that as of late June 2008, over 31,000 patients are now being prescribed Tysabri worldwide, and 13,900 have been exposed to the drug for at least 1 year, and 6,600 exposed for at least 18 months. (Abstract P488)
Reports on Possible MS Risk Factors
• Investigators around the world have been focusing on the question of whether exposure to sunlight (and higher levels of vitamin D the body makes from sunlight) helps explain the fact that MS occurs with higher frequency in regions farther away from the equator. In two presentations, epidemiologist Robyn Lucas, MPH, PhD (Australian National University, Canberra) described early results from a large-scale collaborative, the “Ausimmune Study,” supported in part by the National MS Society (USA) and MS Research Australia.
They have gathered cases of people who’ve experienced a single neurological episode suggestive of central nervous system myelin damage (CIS, and are therefore at risk for developing definite MS) at various latitudes in Australia, and ultimately will track which develop MS. So far they have found early evidence that those cases who had CIS had less cumulative skin damage caused by the sun than the control cases, suggesting they had had less sun exposure. The investigators also found that the incidence of CIS cases increased by 9.2% per higher degree of latitude, and this latitude effect was different for different types of neurological episodes. (Abstracts P551, P552)
• Investigating the sunlight/vitamin D question from the angle of a high-incidence area, researchers at the Hospital for Sick Children (Toronto, Ontario) reviewed records of 35 children with MS from Canada whose serum levels of vitamin D had been tested. Naila Makhani, MD, described finding that only 34% had serum levels considered “adequate” (greater than 70 nmol/L 25-hydroxyvitamin D), while 65% were either “insufficient” (31-69 nmol/L) or deficient (0-30 nmol/L). Future studies are needed to determine whether vitamin D supplementation alters disease susceptibility or course. (Abstract P553)
• In a related study investigating the possible link between vitamin D and risk of MS, reported earlier during the congress, Heather Hanwell, MS (University of Toronto) and colleagues in the Canadian National Pediatric Demyelinating Disease Network investigated 117 children at high risk for MS – youngsters who have had one neurologic episode. They took blood samples and then followed the children for one year or so to determine whether they developed definite MS (as determined by experiencing a second episode). They found that vitamin D levels were significantly lower in the 16% of the children who developed MS. (Abstract 4)
Note: Further studies are needed to determine whether vitamin supplements could reduce the risk of MS, and there is insufficient evidence yet that vitamin D supplements can affect the course of MS once it has begun. Currently , there are well-designed trials in progress that may clarify the potential value and possible risks of vitamin D supplementation in MS within a few years.
More About MS in Children
• Studies from National MS Society-supported Pediatric MS Centers of Excellence and others focus on characterizing MS in this understudied population. John R. Rinker, MD, and others from the University of Alabama-based Center reported that African-American children with MS in general experience more severe disease than children with MS from other racial or ethnic groups. (Abstract P574). The same team reported that out of 45 pediatric MS patients referred to their center over several months, two-thirds had psychiatric disorders in addition to MS. The most common was depression (64%), followed by anxiety and attention deficit hyperactivity disorder. A significant percentage of adults with MS also experience psychiatric disorders such as depression. (Abstract P793)
Progress Identifying Disease Predictors
• Advanced imaging technologies are opening up new windows to the MS disease process and offering hope for better ways to predict individuals’ disease course. Nancy Richert, MD (Neuroimmunology Branch, National Institutes of Health, Bethesda, Md.) described a study that followed 31 people with relapsing-remitting MS over five years, using a variety of magnetic resonance imaging techniques and analyses. They reported that whole-brain magnetic transfer ratio (MTR, a measure of tissue integrity) at entry into the study was more predictive of clinical disability five years hence than were conventional MRI measures, including in individuals who are taking therapies that reduce the number of new lesions. (Abstract 45)
• Results of another study focusing on finding ways to predict the future course of MS were reported by Dr. Bastiaan Moraal (VU University Medical Center, Amsterdam). The collaborators evaluated data from the large-scale clinical trial (BENEFIT study) in which treatment with Betaseron® (interferon beta-1b, Bayer HealthCare Pharmaceuticals) was shown to delay the onset of clinically definite MS in people at high-risk for the disease compared with people who did not receive treatment. In an ongoing follow-up study, the original patients who had been on placebo plus those who had been on active therapy are now receiving Betaseron. Comparing baseline brain MRIs of patients from the start of the study, the investigators were able to discern characteristics that best predicted whose disease would convert to definite MS. The Study was supported in part by the Dutch MS Research Foundation. (Abstract 51)
• Heather Wishart, PhD (Dartmouth Medical School, Lebanon, NH) described a National MS Society (USA)-supported study that uncovered evidence that an alteration in a gene that has been linked to pain perception in healthy adults may also underlie differences in pain perception experienced by people with MS. The study involved 25 people with mild to moderate relapsing-remitting or secondary progressive MS and 12 matched controls. Alterations to this “COMT” gene may increase the amount of the brain messenger dopamine, which in turn may decrease the activity of the body’s natural pain-killing opioids. Further research on the molecular and genetic bases of pain in MS may lead to new therapeutic approaches for this troubling symptom. (Abstract P813)
To view the complete list visit www.msmontreal.org and click on “Scientific Program” and then on “Itinerary Planner” Then follow the prompts.
Betaseron is a registered trademark of Bayer HealthCare Pharmaceuticals
Copaxone is a Registered Trademark of Teva Pharmaceutical Industries Ltd.
Rebif is a registered trademark of EMD Serono, Inc.
Tysabri is a registered trademark of Biogen Idec and Elan
Rituxan is a registered trademark of Genentech and Biogen Idec