Artificially reintroducing a brain chemical called orexin into mice that lack the ability to produce the chemical on their own rids the mice of their narcolepsy symptoms, UT Southwestern researchers have discovered. Their work appears in an upcoming issue of the Proceedings of the National Academy of Sciences and is currently available online.

The genetically engineered mice used lacked a particular type of nerve cell in the brain that produces orexin. Most researchers believe that in humans, a lack of or deficiency in orexin causes narcolepsy, a rare disease in which people uncontrollably fall asleep, have excessive daytime sleepiness, and experience sudden muscle weakness called cataplexy.

"Assuming that narcoleptic humans are like these mice, which is a very plausible assumption, our experiments provide a strong proof of concept that introducing into the brain a molecule that mimics the effect of orexin will be the fundamental cure for human narcolepsy," said Dr. Masashi Yanagisawa, professor of molecular genetics and the paper's senior author.

Orexins are small chains of molecules made by nerve cells, or neurons, in the region of the brain called the hypothalamus. In 2001 Dr. Yanagisawa, an investigator in the Howard Hughes Medical Institute at UT Southwestern, and his research group were the first to genetically engineer knockout mice that lacked orexin-producing brain cells. Without these neurons, the mice did not wake up to feed as normal mice did, and they also experienced cataplectic arrests. "We believe these mice represent the closest model of human narcolepsy," Dr. Yanagisawa said.

In their latest research, Dr. Yanagisawa and his colleagues "rescued" the
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Contact: Amanda Siegfried
amanda.siegfried@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
15-Mar-2004