© ISTOCK.COM/GEORGE PETERSIn the early 1970s, a colleague of Stanford University’s William Dement remarked on the resemblance of a narcolepsy patient’s symptoms to those of a recent canine patient he had read about. The similarity of the symptoms—excessive daytime sleepiness, sudden switch from an awake state to rapid eye movement (REM) sleep, sleep paralysis, and muscle weakness called cataplexy—prompted psychiatrists at the center to track down a narcoleptic dog of their own to study, and then to gather a kennel full of such dogs to figure out what caused the disease. When Dement bred two affected Doberman pinschers in 1976, he found that their narcolepsy was genetic; many of the puppies had episodes of muscle cataplexy and would collapse into sudden sleep, especially when excited.
In 1986, Emmanuel Mignot came to Stanford to work with the narcoleptic dogs, first to evaluate the effects of different narcolepsy drugs and then to tease out the molecular basis of the disorder. More than a decade later he discovered an autosomal recessive mutation in the orexin receptor in the dogs’ brains that was responsible for the disorder (Cell, 98:365-76, 1999). (See “In Dogged Pursuit of Sleep.”) Although orexin receptor mutations have not been found in humans with narcolepsy, patients with the disorder do have reduced levels of orexin (also called hypocretin), a neuropeptide that regulates wakefulness (The Lancet, 355:39-40, 2000).
“The biological basis for orexin mediating wakefulness was pretty strong,” says Joseph Herring, neuroscientist and executive director of the clinical neuroscience program at Merck ...
