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What Causes Narcolepsy?

By Elaine Cassel

Narcolepsy is daytime sleep disorder that usually begins when a person is between fifteen and twenty-five years old. Its sufferers abruptly switch from active, waking states into a few minutes of REM sleep. Until now, the exact cause of narcolepsy has been unknown. But researchers may have found the origins of this mysterious disorder.

The story began last year when researchers noticed that laboratory bred mice (known as "knockout mice" because they are bred to lack certain genes) began falling down in the middle of normal activities like eating and running. They would remain paralyzed for several minutes, and then get up as if nothing had happened--just like people with narcolepsy. DNA analysis of the mice revealed that they lacked the gene for making orexin, a neuropeptide called hypocretin.

Almost simultaneously with this discovery, researchers studying narcoleptic dogs found that they had mutations in the gene responsible for making orexin receptors. The researchers concluded that the dogs' narcolepsy was caused by a mutation in the orexin receptor gene.

DNA studies of people with narcolepsy have found that only a few have mutations in the gene for making orexin or orexin receptors. However, it appears that narcoleptics' brains produce little or no orexin. In one study, 80 percent of subjects had no measurable traces of orexin in the cerebrospinal fluid. Researchers working with the National Institute of Neurological Disorders and Stroke (NINDS), a branch of the National Institutes of Health, studied the brains of four deceased narcoleptics and found that they had lost nearly all of their orexin secreting neurons.

If this line of research holds up, narcolepsy will join Parkinson's disease as the only other known disorder in which a specific type of neurons are virtually absent. Researchers suggest that the administration of hypocretin itself might cure narcolepsy. Now the only treatment consists of amphetamines to keep people from falling asleep and a drug known generically as modafinil.

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