Updated 12:00 PM ET March 28, 2000
By Ariana Murata
(U-WIRE) MONTREAL -- Multiple sclerosis could soon succumb to a barrage of groundbreaking therapies, whose development will involve researchers at the Montreal Neurological Institute.
"In a few months, the MNI will be participating in a large study to determine the potential efficacy of intense immuno-suppression followed by bone marrow transplants as a therapy for MS," said Jack Antel, Chair of Neurology and Neurosurgery at the MNI and associate member of McGill's microbiology and immunology department.
Headed by Mark Friedmann, former MNI researcher and present MS program director at the University of Ottawa, the program will involve first destroying the patient's own immune system. Bone marrow from a healthy donor will then be transplanted into the patient.
Bone marrow produces immune cells. Normally, immune cells protect the body from foreign materials, such as disease-causing bacteria and viruses. When a person has MS, however, their immune cells attack the body's own tissues. By replacing the patient's existing, disease-mediating immune system with healthy bone marrow, the researchers are hoping to generate new immune cells which would no longer attack the body.
Gene therapy could also be a possible treatment for MS. "A definite genetic predisposition for MS has been found," explained Antel. "If a person has MS, there is a 1:100 chance rather than a 1:1000 chance that their sibling will have it. [In comparison], in the case of identical twins, there is a 30 per cent chance that the identical twin will also be affected."
For gene therapy to be a success, the mutated gene or genes causing MS first have to be located. Healthy copies of the gene could then be injected into the body using non-harmful viruses or even immune cells as transport vehicles.
"Early intervention is the key to successfully treating MS," said Antel. "If you can stop the disease before it reaches the secondary progressive MS stage, you could prevent most of the damage from occurring."
Antel's own MNI research lab is studying oligodendrocytes, the brain cells that are destroyed during MS by the body's own "killer" T (immune) cells. Antel and Sandrine Pouly, a post-doctoral fellow, are trying to determine why oligodendrocytes are so susceptible to attack during MS.
Oligodendrocytes produce myelin, a fatty substance that surrounds nerves and helps to conduct nerve impulses with lightning speed. By understanding oligodendrocyte biology, Antel foresees a possible future therapy for MS that could involve regeneration of oligodendrocytes, re-myelination of nerves, and possibly, full restoration of nerve function.
Along with Alex Prat, a neurology resident and winner of the 2000 S. Weir Mitchell Award from the American Academy of Neurology, Antel is also examining how lymphocytes interact with the blood-brain barrier. The lymphocytes are transported from the bone marrow (where they are generated) to the brain via the bloodstream. In order to enter the brain, the lymphocytes must basically "chew" their way through the blood-brain barrier, using special enzymes known as proteases.
The most common type of multiple sclerosis is relapsing-remitting MS. RRMS affects about 100 in every 100,000 Canadians. In RRMS, symptoms such as fatigue, weakness, and trouble with balance will appear for several weeks, then disappear. In between MS attacks, patients will make a full recovery.
Up to 50 per cent of those affected with relapsing-remitting MS will eventually develop secondary progressive MS. This is typified by attacks that continually increase in severity. In between attacks, the patient will not recover fully. Serious, permanent disability can result.
At the present, there are two drugs available for treating MS: Interferon- (IFN-) and Copaxone. They have both been successful at decreasing the number and severity of MS attacks that patients will experience. Before their wide-scale emergence in the early 1990s, there was no effective treatment for MS.
"[During MS attacks] I would lose my balance and feel a weakness in my legs," said Lise Champagne, a Montreal resident. "When I tried to speak, my voice would be weak and soft. I couldn't speak loudly, even when I tried. I would feel very tired."
Champagne was diagnosed with MS in 1993. She was forced to resign from her job at a glass company. For many years, she had no treatment available and would suffer one to two MS attacks each year. A momentous change came into her life last September when she began to take IFN-.
"I find Interferon- terrific," says Champagne. "I feel less tired and I've had no attacks so far. I'm just keeping my fingers crossed."
Champagne must inject herself with IFN- every two days. When she first started taking IFN-, she experienced flu-like symptoms and would fall asleep at dinnertime. She now takes IFN- in the evening, before bedtime, and no longer experiences any adverse side effects.
"I used to go to Florida a lot, during the summer and during the winter," says Champagne, reminiscing about her pre-MS days. "I really liked to go swimming there. Maybe, I could go back some day."
Dr. Antel's oligodendrocyte work is being funded by the Medical Research Council of Canada. The Multiple Sclerosis Society of Canada is financing his research on the interactions between the immune and nervous systems.
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