New Treatment for MS May Be Ahead
drkoop.com Health Correspondent
On television's The West Wing, fictional U.S. president Jed Bartlet struggled to balance the pressures of a re-election campaign and the symptoms of multiple sclerosis. In real life, some 300,000 Americans who have MS struggle withfatigue, tingling, numbness, painful sensations, blurred or double vision, muscle weakness, impaired balance, spasticity, tremor, changes in bladder, bowel, and sexual function, cognitive changes such as forgetfulness or difficulty in concentrating, speech and swallowing. Martin Sheen, who portrays Bartlet on the award-winning weekly series, can walk away from the set and leave his role of MS patient behind, but, for now, he's the only one with that option. New research from the National Institute of Allergy and Infectious Diseases (NIAID), however, suggests that effective treatments for the disorder may be on the way.
Immune Suppression Without Toxic Side Effects
The new approach -- like many current treatments for the disease -- directly targets the cause of MS -- which is believed to be an immune system's cells gone awry. But, the latest therapy would have a benefit over existing approaches, according to its discoverers. "Current treatments for MS broadly suppress the immune system and can cause toxic side effects," says Michael Lenardo, M.D., of NIAID's Department of Immunology. "This treatment, called antigen-specific immunotherapy, specifically targets the immune system's T-cells that cause the disease. Presumably, it would not lead to such side effects." Lenardo and his colleagues announced results of their preliminary use of the therapy in the February 1 issue of Journal of Immunology.
Multiple Sclerosis: T-Cells on a Rampage
Doctors think MS occurs in humans when certain white blood cells in the immune system called "T-cells" mistakenly attack myelin sheaths, the protective coverings that surround and insulate signal-carrying fibers of nerve cells. When these myelin sheaths are destroyed by rampaging T-cells, the nerves can no longer conduct electrical impulses normally, and the symptoms of MS are stimulated.
According to Loren A. Rolak, M.D., medical advisor of the New York City-based National Multiple Sclerosis Society, MS is one of the most common diseases affecting people of all ages worldwide, but it has a special preference for young people, especially women, and for those who grew up in northern latitudes.
"We believe MS involves a genetic susceptibility," says Rolak, "but the disease is not directly inherited. It usually causes sudden neurologic symptoms, and these symptoms can be diverse and confusing, often coming and going without any pattern, making it difficult to diagnose, even today." "The specific triggering mechanism which causes an immune system to attack its own myelin remains unknown," Rolak continues. "But a viral infection on top of an inherited genetic susceptibility is a leading suspect."
Turning the Tables on T-Cells
The experimental approach to treating MS developed by Lenardo and his colleagues at NIAID makes use of a discovery the researchers made about what seems to set T-cells off on their mission of destruction. Using marmoset monkeys as their subjects, the scientists found that when T-cells were exposed to small amounts of the proteins that make up the myelin, an attack was stimulated.
The biggest news, however, was that the NIAID team discovered if the same T-cells were exposed to large amounts of this same protein, they tended to "self-destruct." Leonardo reasoned that if large amounts of myelin proteins were introduced into the body, the T-cells causing the de-mylenization would be destroyed -- and the MS would be halted.
"The therapy is counter-intuitive," explains Lenardo. "One might think it would be like pouring gasoline on a fire. But the self-destruct sequence actually protects the body from having too many active T-cells, which can themselves be toxic.Like any potent weapon, you want to control how much is deployed. The immune system doesn't let your T-cells grow uncontrolled and kill you.In this case, adding more antigen smothers the fire." This approach to disease control goes by the name "antigen-specific immunotherapy."
Antigens are substances that cause the formation of an antibody or elicit a cellular response in a living organism. In autoimmune disorders, the antigens often provoke the T-cells, which has long been known to be a cause of many human illnesses, although it's only recently been considered a potential solution as well.
As recently as the mid-1990s, the use of antigens to treat conditions such as MS was unheard of.For instance, Hugh O. McDevitt, professor of microbiology, immunology and medicine at Stanford University, reported at the 1995 meeting of the American College of Rheumatology, "antigen-specific immunotherapy bears no resemblance to any current therapy." In the six years since, however, antigen-specific immunotherapy research similar to that undertaken by Lenardo and NIAID for MS has been focused on several immune system conditions, such as rheumatoid arthritis, diabetes and myasthenia gravis, as well as for certain cancers. And antigen-specific immunotherapy has emerged as a very promising avenue of treatment in many. "Immune-mediated diseases are a major cornerstone of the NIAID research effort," says Anthony S. Fauci, M.D., director of the NIAID, one of the federally funded National Institutes of Health. "Efforts such as Dr. Lenardo's hold great promise for developing new treatments for individuals with autoimmune diseases."
Too Early to Celebrate
Despite the promising news, Stephen Reingold, Ph.D., vice president for research at the National Multiple Sclerosis Society, cautions that it's still a little premature to "jump up and down in celebration that antigen-specific therapy as a definitive treatment for MS is just around the corner."
"NIAID's research is promising in that it provides us with more information about how antigen-specific therapy can work in another animal model," he explains. "Obviously the whole concept is an important one and well worth developing, but as for an acceptable treatment that will work for MS in human beings -- let's just say we aren't quite there."
Reingold notes that scientists still have to identify the specific antigen or antigens in human beings that prompt the immune system response; then, a way of safely testing it in clinical trials must be devised. All of this must occur before any treatment based on the work of Lenardo and his team is generally available for MS patients.
"It's a complex process," says Reingold. "Although antigen therapy is a terrific idea, it probably will be directed first to diseases in which a single specific antigen is known. MS may involve several antigens, and hitting one may not be all that helpful. Or different individuals with MS may have different antigens responsible for their symptoms. At this point we just can't say how much impact this line of therapy will have -- if any."
Date Published: 7/6/01
Date Reviewed: 7/9/01