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Hypocretin deficiency may cause narcolepsy
  
By Christina A. Pan

Researchers believe that low levels of a protein called hypocretin may be an underlying cause of narcolepsy—a disorder that makes people fall asleep during the day. Pharmaceutical companies are now looking for drugs that will replenish the lost hypocretin.

Emmanuel Mignot, of Stanford University Medical School, California, and his colleagues found low levels of hypocretin in patients with narcolepsy and in the brains of narcoleptic people who died of unrelated causes. The results of the study appear in the September issue of Nature Medicine.


Pair of Doberman pinschers playing (top); seconds later they have a narcoleptic attack (bottom).

Currently there is no cure for narcolepsy. The classic symptoms include the uncontrollable desire to sleep during the day, sudden loss of muscle tone, and paralysis. Often diagnosed in people aged 15 to 25, those affected by the disorder must find ways to cope with the interruptions in normal behavior by changing their work and eating habits.

Initially, Mignot studied dogs that had low levels of hypocretin. The gene and receptor for hypocretin were identified as well as a genetic mutation that occurred in dogs with narcolepsy. In his recent study, Mignot found that people suffering from narcolepsy have the gene and receptor for hypocretin, however, in all but a single case, the mutation is not present.

In another study, researchers at the University of California, Los Angeles, found that patients with narcolepsy have a dramatic and degenerative loss of the brain cells containing hypocretin.

The reason for this loss is still a mystery. Mignot suspects that the death of hypocretin-producing cells may come from an autoimmune condition. New medicine would bring relief to many with this disorder, which affects about 135,000 people in the United States.

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To download the movie of narcoleptic dogs visit Stanford University Center for Narcolepsy's website: http://www-med.stanford.edu/school/Psychiatry/narcolepsy/moviedog.html

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Peyron, C. et al. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin in human narcoleptic brains. Nat Med 6, 991-997 (September 2000).
 
Thannickal, T. et al. Reduced number of hypocretin neurons in human narcolepsy. Neuron 27 (September 2000).
 

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