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The Atlas of MS, providing data on MS around the world, was introduced on the second day of the first World Congress on Treatment and Research in MS, along with novel strategies to repair MS damage, new data on children with MS, and updates on alternative interventions. The congress, being held this week in Montreal, Quebec, is the largest international conference on MS research and treatment in 2008.
During the Plenary session, the Don Paty Memorial Lecture by Dr. T. Jock Murray (Dalhousie University, Halifax, Nova Scotia) provided an outstanding overview of progress made over the decades in our understanding of MS. Summing up this progress, he said, “We are moving from a negative era of despair to an era of hope and inspiration for people with MS.”
A major effort has been launched to reach out to people with MS in all corners of the globe, and gather the data necessary to provide the best health care services and form the best health care policies. Alan J. Thompson, MD, FRCP (National Hospital for Neurology and Neurosurgery, London) and colleagues unveiled the Atlas of MS, a joint venture of the World Health Organization and the MS International Federation. The largest ever international survey of its kind reached people in 112 WHO member states, area and territories, representing 88% of the world’s population, to gather data on MS prevalence and the resources available to diagnose, treat, and support people with MS.
The Atlas highlights the need for changes to improve MS care, including efforts to better inform the public and health professionals about the disease, and the need to make health services specific to MS more available and accessible. Survey results are presented in charts, maps and text on the Web sitewww.atlasofms.org. (Abstract #P423)
Repairing disease damageis an elusive goal of MS research – thanks to treatments currently on the market, we can often do a reasonable job of stopping the immune attack on the brain and spinal cord, but we still can’t repair the damage it causes. Today, research teams from around the world reported their strides forward in this important aim.
Evidence that an approved therapy,Copaxone® (glatiramer acetate, Teva Pharmaceutical Industries), may contribute to neural health was reported today based on a subgroup of the PreCISe study (in which the drug reduced the risk of developing MS and delayed the development of MS among individuals with CIS – clinically isolated syndrome – a first event suggestive of MS). Douglas L. Arnold, MD (NeuroRx, Montreal) and colleagues used magnetic resonance spectroscopy to examine levels of NAA – a marker of nerve fiber integrity – in a subgroup of 34 people. These levels were significantly higher in people taking Copaxone compared to those on placebo at one year. (Abstract #17)
One experimental strategy under study for repairing tissue damage in MS is cell transplants, such as “mesenchymal stem cells” which are derived from bone marrow. Antonio Uccelli, MD (University of Genoa) studied whether mesenchymal cell transplants would affect the immune attack as well as tissue damage in mice with the MS-like disease EAE. Despite finding little evidence that these cells developed into actual replacement nerve cells, they found evidence that brain tissue was protected from disease, as well as an increase in T cells that regulate the immune attack and a decrease of pro-inflammatory cells. (Abstract #27) Results of an early clinical trial of mesenchymal stem cells are slated to be presented during the conference on September 19.
People with MS have varying symptoms, which means that the underlying damage probably differs as well, and understanding these differences is a vital first step to devising repair strategies. A. Giorgio, MD (University of Siena, Italy) and colleagues examined changes in brain volume over an average time period of 18 months using MRI in 963 people with different types of early and later MS who were involved in placebo arms of clinical trials or who were not taking any disease-modifying therapy. Using a new technique to analyze brain atrophy, the investigators reported that reductions in brain volume were similar in people in the earliest stages of MS as to those in late stages. They concluded that this damage occurs steadily during the disease’s evolution. Further work is needed to verify these findings over longer periods of time. (Abstract #16)
Dr. Hanneke Hulst (VU University Medical Center, Amsterdam) and colleagues reported on a posthoc analysis of data compiled during year one of a clinical trial of the experimental oral therapy ibudilast (MN-166, MediciNova, Inc) involving 297 people with relapsing MS. They found that the relative proportion of acute inflammatory lesions – detected on MRI scans – that evolved into destructive lesions (defined as persistent black holes on MRI scans) was significantly reduced in the treated group compared with the placebo group. This suggests a possible neuroprotective effect of this drug. (Abstract #P271)
Now that MS therapies have been on the market for more than 15 years, researchers continue to report on their long-term safety and efficacy. Robert Bermel, MD (Cleveland Clinic Foundation) and colleagues reported on an open-label, multicenter, 15-year follow-up survey of participants in the pivotal phase 3 trial that led to the approval ofAvonex® (interferon beta-1a, Biogen Idec) for MS. Of the original 172 participants who completed the original study, 136 were included in this study, and of those 14 were deceased. The data were compiled via questionnaires. About half are still using Avonex, for a median of 13.3 years. 89% of these long-term users stated that their health was good to excellent, and significantly fewer long-term users had reached a disability status score (EDSS) of 6.0 (a score indicating that a person needs intermittent support with a cane or other device to walk) compared with other participants. (Abstract #P14)
People with MS who share anecdotes about the success of dietary supplements, or other alternative therapeutic strategies, are often frustrated by the answer, “There are not enough data to support the use of this treatment.” At the conference, several groups reported such data on MS therapeutic strategies somewhat off the beaten path.
Growing evidence is linking increased levels of vitamin D to decreased MS risk, but one question is, "Will vitamin D supplements protect people from developing MS?" First, we’d need to know the safety of increasing supplementation in people with MS. Jodie Burton, MD (St. Michael’s Hospital, Toronto) and colleagues compared administering escalating doses of vitamin D3 (the equivalent of 4,000 to 40,000 international units per day) to 25 people with MS over 52 weeks, with 24 untreated controls. Calcium levels remained within normal limits. Immune system analysis showed that reactivity of T cells – major players in the MS attack – was reduced. Trends toward clinical improvement were noted, but they were not significant. The group is now planning a phase II study of vitamin D supplementation that will focus on MRI and clinical endpoints. (Abstract #P20)
Ikuo Tsunoda, MD, PhD (University of Utah, Salt Lake City) and colleagues administered resveratrol, a component of red wine, to mice with an MS-like disease induced by a virus. Resveratrol enhances the activity of SIRT1, a molecule that might help to preserve nerve fibers. In this National MS Society-funded effort, treated mice gained more weight than untreated mice, a sign of clinical improvement that the researchers say might be attributed to nerve protection. In mice infected with a low dose of virus, fewer died with resveratrol treatment. The team is proceeding with the pathologic studies necessary to confirm this hypothesis. (Abstract #P212)
Although exercise is helpful in managing many MS symptoms, research on the type and intensity of this exercise continues. Heather Hayes, DPT (University of Utah, Salt Lake City) and colleagues were funded by the National MS Society to compare a standard exercise program with a high-intensity resistance training program in 19 people with moderately severe MS. There were no significant differences in the improvement of strength or mobility between the two programs –fatigue improved significantly in both groups. The results showed no significant additional benefit of this high-intensity program for people with moderately severe MS – such studies help to direct exercise protocols for people with this disease. (Abstract #P385)
Generally, the risk of MS in African Americans is around half that of Caucasian Americans, but research indicates that African Americans tend to have a more aggressive course of the disease. Omar Khan, MD (Wayne State University) and colleagues, funded by the National MS Society, compared the presence of antibodies in the spinal fluid of 150 African Americans with MS and 150 Caucasians with MS, finding increased levels of antibody production among the African American population, and demonstrated correlations between antibody production and central nervous system tissue destruction. This study provides evidence that immune B cells may be responsible for exaggerated signs of inflammatory tissue destruction in African-Americans (as opposed to T cells, often blamed as the prime soldiers in the immune attack). (Abstract #P347) Studies of B cell depletion therapies are underway.
Data are accumulating on the impact of MS in children, thanks to a worldwide network focused onpediatric MS. Emmanuelle Waubant, MD, PhD (Pediatric MS Center of Excellence, San Francisco), funded by the National MS Society, presented a study of 31 individuals whose onset of MS was in childhood versus 31 whose disease began in adulthood. Her team found that children at disease onset carry a higher disease (lesion) burden, as measured by MRI brain scans, than adults at disease onset. (Abstract P290)
Researchers at the National MS Society-funded Pediatric Center of Excellence in Stony Brook, New York, reported on a study of fatigue in 51 children with pediatric MS. William Macallister, PhD, reported that fatigue was a major MS symptom for 43% of these children, who can experience this symptom even early in the disease and in the absence of other significant neurologic impairments. Fatigue can impact school performance and other quality of life issues. (Abstract P397)
Mark Gorman, MD (Massachusetts General Hospital, Boston) presented a study comparing disease characteristics of adults with MS and children seen at their National MS Society-supported Pediatric MS Center of Excellence. They found that relapses were more frequent in the pediatric group, despite data that disease progression appears to be slower in pediatric-onset MS. (Abstract P128)
MS typically initially affects women of childbearing age. When young women receive a diagnosis of MS, they frequently have questions about theeffects of the disease on childbearing, and vice versa, making this a crucial area for research. Some brief findings reported today in this area include:
• Dr. M. Mendibe (Hospital de Cruces, Baracaldo, Spain) and colleagues analyzed the evolution of disability in 451 women with MS and showed that having children did not affect the development of disability. (Abstract #P99)• Annette Wundes, MD (University of Washington, Seattle) and colleagues analyzed data from 391 women with MS and showed that significantly fewer have children than the U.S. national average. It is not clear whether this is the result of biological factors or choice. (Abstract #P428)• Chiara Rivoiro, MD (S. Luigi Gonzaga Hospital, Orbassano, Italy) and colleagues administered gonadotrophin releasing hormone (GnRH) -analogue treatment to 12 women undergoing treatment with mitoxantrone to prevent onset of premature ovarian failure – a common long-term consequence of similar chemotherapeutic agents. So far, six women have completed treatment with both agents and have returned to normal menstrual cycles. (Abstract #P446)
To view the complete list, visitwww.msmontreal.organd click on “Scientific Program” and then on “Itinerary Planner”. Then follow the prompts.
Avonex is a registered trademark of Biogen Idec.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.
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