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Researcher IDs Narcolepsy as Autoimmune Disease
Date:5/4/2009

Discovery of 2 gene variants that kill off protective hormone could lead to new treatments

MONDAY, May 4 (HealthDay News) -- Stanford University researchers say they have determined that the sleep disorder narcolepsy is actually an autoimmune disease.

The finding, published in the May 3 online issue of Nature Genetics, links narcolepsy to mutations of two genes involved in critical roles in protecting the body from disease. These two variations, they say, are likely conspirators against hypocretin, a hormone that promotes wakefulness, and that narcoleptics have been found to lack.

Narcolepsy causes excessive drowsiness, to the point of the person having brief but sudden bursts of sleep during the day. The condition, which affects about one in 2,000 people, also causes poor nighttime sleep patterns and even cataplexy -- a sudden loss of muscle tone and strength.

"This is a very important finding," sleep disorder expert Merrill Mitler, program director at the U.S. National Institute of Neurological Disorders and Stroke, said in a Stanford news release. "It puts in place another piece of the puzzle and shows a way to link [this gene variant] to hypocretin-containing neurons via an autoimmune attack."

The researchers conducted genetic studies on 1,800 people with a variant for the human leukocyte antigen, or HLA, gene, which helps the immune system identify foreign bodies it needs to eliminate to protect the body. Previous studies had linked the HLA variant to narcolepsy, a condition nearly half the study subjects had.

The Stanford team found that all the study participants with narcolepsy also had a mutated gene link to T-cells, which are vital cogs in all the body's immune responses.

Dr. Emmanuel Mignot, director of Stanford's Center for Narcolepsy, said it's likely that HLA and the T-cell variant interact in a way that kills hypocretin cells, although his team's findings did not determine that direct relationship.

"For a long time, people have suspected narcolepsy had something to do with the immune system -- that it was killing cells that produce hypocretin," Mignot, a professor of psychiatry and behavioral science, said in the news release. "But there hasn't been direct proof. Our discovery clearly shows narcolepsy is an autoimmune disease."

If further study can reveal the two mutations work together, scientists may be able to later identify people predisposed to narcolepsy and find ways to prevent its development, he said. It may also lead to discoveries concerning other more common autoimmune afflictions such as multiple sclerosis and juvenile diabetes.

More information

The U.S. National Institute of Neurological Disorders and Stroke has more about narcolepsy.



-- Kevin McKeever



SOURCE: Stanford University School of Medicine, news release, May 3, 2009


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