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MS gene discovery: a piece of the puzzle.

MS gene discovery: A pirce of the puzzle

A specific gene can heighten a person's risk of multiple sclerosis (MS),say scientists who have identified the gene and confirmed its link to the disease. Because the gene plays an important role in the function of certain immune cells, called T-cells, its discovery supports the hypothesis that a malfunctioning immune system causes the disease. If researchers can determine which part of the gene is linked to MS susceptibility, "the specific destruction of the T-cells which use that piece may be possible," says study coauthor Stephen L. Hauser of Massachusetts General Hospital in Boston. Such therapy has already succeeded in MS-afflicted mice, suggesting it's a realistic possibility in humans, he says.

Researchers have long suspected a genetic component in multiple sclerosis. Studies have demonstrated, for instance, that a person whose identical twin suffers from multiple sclerosis is at much higher risk for the disease than is another sibling. More recently, researchers have associated certain forms of the T-cell gene with multiple sclerosis in individual patients. Until now, however, no one had viewed the gene in its entirety or demonstrated its link to multiple sclerosis by showing its inheritance pattern in families, Hauser says.

Although the finding advances the study of multiple sclerosis, there are "probably 50 pieces in the MS puzzle," says Howard L. Weiner, head of MS research at Brigham and Women's Hospital in Boston. "This is one of the pieces . . . but it isn't the answer."

Hauser's work, described in the June 30 CELL, shows that people who carry specific forms of the identified gene run 3.3 times the MS risk of the general population. However, previous studies indicate that the risk faced by siblings of MS patients is fully 20 times that of the general population. For this reason, Hauser's team says that several genes, and perhaps one or more environmental factors, appear likely to be involved.

Multiple sclerosis destroys the fatty sheath of myelin surrounding nerve-cell axons, disrupting nerve transmission and producing varied and changing symptoms including weakness, tremors and impaired vision (SN: 10/10/87, p.234). Although the cause of the myelin destruction remains unknown, scientists suspect that multiple sclerosis reflects an immune system gone haywire, with misguided T-cells attacking the body's own tissues.

The T-cell hypothesis led Hauser and his team to look for an abnormality in a gene coding for a protein receptor that enables a T-cell to recognize its target. They used a refined form a technique called pulse-field gel electrophoresis -- which allowed them to view the whole gene unbroken -- to "unequivocally identify the unique nature" of the two T-cell gene copies in 40 sibling pairs in which both siblings had multiple sclerosis, Hauser says.

They found that 15 of the sibling pairs had inherited the same two forms of the T-cell receptor gene from their parents and that only three pairs shared neither gene copy. This distribution differs significantly from what scientists would expect from a random sample of individuals. If the genes were not linked to the disease, Hauser explains, 10 of the 40 sibling pairs should carry the same two gene copies from their parents, 20 should have in common one of these copies, and 10 should have neither copy in common. Indeed, the researchers say they found exactly this ratio in their eight control families and in a comparison of MS patients with unaffected siblings.
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Title Annotation:multiple sclerosis
Author:Wickelgren, I.
Publication:Science News
Date:Jul 8, 1989
Words:566
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