October 29, 2003
The National Multiple Sclerosis Society
The eighth annual meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) was held in San Francisco on October 19, immediately preceding the American Neurological Association's annual meeting. The meeting was chaired by Dr. Kenneth P. Johnson and jointly sponsored by the National Multiple Sclerosis Society and the University of Maryland School of Medicine, in collaboration with the MS Society of Canada.
International MS experts presented findings to an audience of 270 MS-specialist physicians, basic scientists and clinical investigators. The ACTRIMS program provided a forum where these three interrelated groups were able to exchange information and discuss research findings in order to speed the pace of scientific discovery and improve patient care.
You can find the abstracts of all presentations posted on the ACTRIMS website at www.actrims.org. Here are just a few of many highlights from the ACTRIMS 2003 program:
Studying Primary-Progressive MS
In the Keynote Address, Jerry Wolinsky, MD (The University of Texas Health Sciences Center) reviewed data from the PROMISE trial, a study of Copaxone® (glatiramer acetate) aimed at slowing progression of disability in people with primary-progressive MS (PP MS, which slowly but nearly continuously worsens from onset). An interim analysis of results showed no possibility of demonstrating a treatment effect, perhaps because the untreated placebo group did not progress significantly over the time of study, and the study was therefore discontinued in late 2002.
The investigators decided to review all data to evaluate if there might have been a subgroup of individuals in the study who showed greater progression, and who thus might have been a better group to test in this trial. Dr. Wolinsky and colleagues analyzed the results from this trial involving 943 patients, identifying several clinical and imaging factors that might have enabled the investigators to identify more clearly disease progression. If these results are verified, such study ”enrichment” factors may prove invaluable in planning future studies to evaluate treatment success in people with primary-progressive MS, a type of MS for which there is as yet no approved treatment.
Can the Immune System Protect the Nervous System in MS?
MS occurs when the immune system attacks the brain and spinal cord. The inflammatory events are generally considered to be uniformly damaging to nervous system tissues. However, Michal Schwartz, PhD (The Weizmann Institute of Science, Rehovot, Israel) is focused on inflammatory and other immune events that might be “protective” as well as destructive in diseases like MS. Her team has shown that immune T cells programmed to attack the central nervous system may also home in to the site of damage and help brain cells to reduce nerve degeneration. To study this, the team injected immune cells activated against a myelin protein up to 12 days after spinal cord injury in rats. The “vaccinated” animals experienced significant and pronounced recovery from injury. Dr. Schwartz noted efforts underway to develop a vaccine with such myelin proteins that could establish a protective autoimmune response without bringing on autoimmune disease.
More Imaging Findings from Estriol Trial in Women With MS
Nancy L. Sicotte, MD, a Harry Weaver Neuroscience Scholar of the National MS Society, and colleagues (University of California, Los Angeles) extended the findings of a small-scale, early-phase trial of the hormone estriol, a form of estrogen, in which women with relapsing-remitting MS showed decreases in areas of myelin damage (lesions) and immune responses during treatment. Dr. Sicotte reported that the rate of severe “black holes” detected with magnetic resonance imaging – dark areas that indicate nerve tissue damage – appeared to slow during estriol treatment, and areas of myelin damage identified during the study did not evolve into severe black holes. These results suggest that the hormone therapy might have an impact on the development of brain lesions that are considered to be the hallmark of MS. The team is hoping to conduct a larger, longer-term trial of estriol in MS.
A New Target for MS Treatment
Heike Wulff, PhD (University of California, Davis) and colleagues have found a striking difference in the patterns of ion channels – tiny pores – on immune T cells from people with MS and people without MS. They have also shown that a protein that blocks these pores can prevent MS-like disease in rats. In a new study using T cells that react to myelin, taken from people with MS, the group reported that one particular ion channel may be repeatedly stimulated throughout the course of disease. With funding from a Society Pilot Research Award, Dr. Wulff and colleagues are now developing a compound to inhibit this ion channel in hopes of stopping MS-like disease in animal models, a first step to applying such approaches as a treatment for MS itself.
Protecting Nerve Cells from Death
Steven W. Levison, PhD (Pennsylvania State University, Hershey) and colleagues have shown that levels of a protein known as ciliary neurotrophic factor, or “CNTF,” are elevated in the spinal cords of mice with an MS-like disease, specifically during their recovery from disease. At ACTRIMS, they report further on this molecule, noting that survival of brain cells increases when treated with CNTF, and that the molecule does so indirectly, by inducing production of similar “growth factor” molecules known as FGF-2 and IGF-1. This Society-funded effort is providing key information to developing strategies that promote myelin repair in MS.
Less Fibrin, More Nerve Tissue Repair
Katerina Akassoglou, PhD (University of California, San Diego) and colleagues
are studying the role of fibrin, a natural substance that is deposited
at sites of myelin damage in MS, with funding from the Society. Their findings
have indicated that fibrin, an essential component for healing wounds,
may inhibit myelin repair. Now they report the results of administering
a fibrin-depleting agent to mice with the MS-like disease EAE. Treated
mice recovered from an initial attack of disease faster than untreated
mice, and never relapsed, showing a 10-fold increase of motor strength
and coordination. Further study will determine the potential for fibrin-depleting
agents to treat MS.
Copyright © 2003, The National Multiple Sclerosis Society