Health: Using human antibodies, researchers are able to regrow nerve sheaths in mice with a similar disease. Expert says it is first step toward cure.
Tuesday, June 6, 2000 | LA Times
By THOMAS H. MAUGH II, Times Medical Writer
Researchers have for the first time been able to significantly repair central nervous system damage in mice that have a disease that mimics multiple sclerosis, a finding that eventually may lead to new treatments for the crippling disorder.
In MS and several related diseases, the myelin sheath that surrounds nerve fibers and protects them like the insulation on an electrical wire breaks down, allowing the nerves to "short-circuit," destroying muscle control.
But giving two human antibodies to mice with the disease causes the myelin to regrow, Dr. Moses Rodriguez of the Mayo Clinic said Monday. His team reports its results in today's Proceedings of the National Academy of Sciences.
Scientists previously had thought that damage to myelin was permanent and that repair was not possible, so demonstrating the ability to grow new myelin represents a major change in thinking about potential treatments.
"This is not a cure for MS, but a very important first step toward a cure," Rodriguez said. "Our goal now is to get into clinical trials as soon as possible," but that may take several years, he said.
"Yes, this is headed in that direction [human trials], but there is a lot more preclinical work to do," said Dr. Steven Reingold, medical director of the National Multiple Sclerosis Society. "We won't know if this can be used in humans until we do those studies."
Multiple sclerosis is an unpredictable, chronic and often disabling disease of the central nervous system that affects as many as 350,000 Americans. Symptoms can include fatigue, impaired vision, loss of balance and muscle coordination, slurred speech, tremors, stiffness and, in the most severe cases, partial or complete paralysis.
Most researchers now believe that MS is an autoimmune disease triggered by an infectious agent such as a virus. The theory is that a viral protein that resembles myelin triggers an immune reaction that strikes not only the virus, but the body itself.
Most MS treatments now are directed at suppressing this immune response. Such treatments can delay progression of the disease but do not repair any damage to the myelin.
But the conventional wisdom about the cause of MS has been brought into question by a separate report in Saturday's Annals of Neurology. By closely examining damage--or lesions--to myelin in 53 patients, an international team concluded that MS may actually represent as many as four different diseases, each with its own pattern of damage, its own cause and its own clinical outlook.
That may explain why new treatments often dramatically benefit some patients, while other patients show no improvement, Reingold said. The National MS Society is now launching a "Lesion Project" in an attempt to correlate lesion patterns with disease progression and responsiveness to therapy.
Rodriguez and his colleagues used a mouse model of MS that is triggered by infecting the animals with an unusual virus called Theiler's murine encephalomyelitis virus. The infected animals develop a disease that is very similar to human MS and that responds to MS therapy in the same ways that humans do.
The team screened hundreds of human antibodies to identify two that bind to oligodendrocytes, cells from the central nervous system that actually produce myelin.
They report that treating the mice with the antibodies for five weeks caused myelin to regrow. Over that brief period, new myelin repaired about 25% of damaged areas of the spine.
Because the mice were killed to examine their spinal cords, the team was not able to observe whether there were corresponding improvements in limb function. "We're looking at that very intensively right now," Rodriguez said.
Rodriguez speculated that the antibodies bind to oligodendrocytes and stimulate them to undertake the needed repairs. Alternatively, they may simply remove damaged myelin, thereby triggering repair.
"How it works and why it works, we are not 100% sure," Reingold said.
The antibodies that were used were isolated from patients with Waldenstrom's macroglobulinemia, a type of lymphoma in which the body produces large amounts of a single antibody. No one knows what these particular antibodies normally do, but the fact that they are present in the donors in high quantities without producing any known effects suggests that using them in human therapy could be safe.
Molecular biologist Larry R. Pease, a member of the Rodriguez team, decoded the genes for making the antibodies so that they can be produced artificially.
Acorda Therapeutics of Hawthorne, N.Y. is now gearing up to manufacture enough of the antibodies to allow clinical trials, but that will take some time, said company President Ron Cohen. The new antibodies also will have to be tested for toxicity, further delaying the effort.
Further information about the study is available at the Mayo Web site
(http://www.mayo.edu) and at the Acorda
Web site (http://www.acorda.com).