In the first study to pinpoint the cause of narcolepsy in humans, UCLA/VA researchers report in the September issue of the peer-reviewed journal Neuron that the dramatic, degenerative loss of a specific type of brain cell triggers the debilitating sleep disorder.

Hcrt cells, or neurons containing the neuropeptide hypocretin, are located exclusively in the brain's hypothalamus. Hypocretin sends messages to numerous regions throughout the central nervous system, including the major mass of cells that regulates sleep.

The researchers found that the number of Hcrt neurons in narcoleptics was 85 percent to 95 percent less than the number found in non-narcoleptic brains.

Other types of neurons that intermix with Hcrt cells in normal brains were not reduced in number in the narcoleptic brain, indicating that cell loss was confined to Hcrt neurons. In addition, the presence of gliosis, or neural scarring, in the hypocretin cell region indicates a degenerative process.

The discovery suggests that the replacement of missing hypocretin neuropeptides produced by Hcrt cells may reverse some of the symptoms of the incurable disease.

"The findings end a 120-year search for the cause of narcolepsy and open new paths for treating this incurable disease," said Dr. Jerome M. Siegel, professor of psychiatry and biobehavioral sciences at UCLA, chief of neurobiology research for the Greater Los Angeles Veterans Affairs Healthcare System, and senior author of the study. "While it is clear that the degenerative loss of Hcrt cells is directly linked to narcolepsy, the cause of this cell loss remains to be determined. An autoimmune attack on Hcrt neurons or a sensitivity of the cells to specific environmental or biological toxins are possibilities."

Narcolepsy affects approximately 1 in 2,000 individuals (about 125,000 in the United States) and usually develops in young adults in their 20s and 30s, progressing over a period of one or two years and then stabilizing.

The disease causes overwhelming sleepiness and cataplexy, a loss of muscle tone triggered by sudden strong emotions such as laughter and impulsive anger. Most narcoleptic patients experience sleepiness rather than cataplexy.

Narcoleptics go through life feeling the way most individuals would feel after staying awake for 48 hours. They awake refreshed from naps but soon feel sleepy again. Their nighttime sleep is fragmented, with fewer of the deeper stages of sleep.

-UCLA-

DP396