Narcolepsy Linked to Brain Cell Loss
W A SH I N G T O N, Aug. 29 -- Narcolepsy, a disorder thatleaves tens of thousands of people constantly groggy and someunable to work, could be caused by the loss of specific braincells, U.S. researchers said today.
People with narcolepsy have lost nearly all of the neuronsthat secrete a particular message-carrying chemical calledhypocretin, a team at the University of California, LosAngeles, (UCLA) found.
Another team at Stanford University confirmed that peoplewith narcolepsy are lacking hypocretin.
This could lead to an effective treatment for thecondition, which affects about one in every 2,000 people, orsome 135,000 Americans, said Cheryl Kitt, a sleep disorderspecialist at the National Institute of Neurological Disordersand Stroke (NINDS).
A Clue to Treatment
“The excitement is that it finally gives us a clue to wheretreatment may occur,” Kitt said in a telephone interview.
“It is possible in the future that the administration ofhypocretin itself might be a treatment for narcolepsy,” addedKitt, who approved NINDS funding for the two studies.
She said researchers were already starting studies inanimals.
“It is very unusual in neurology to find a very specificgroup of nerve cells that are missing in a disorder,” Kittsaid. Parkinson’s disease, in which cells that produce dopamineare mistakenly destroyed by the body, is another rare example.
Psychiatrist Jerome Siegel of UCLA and of the Veteran’sAffairs Medical Center in Sepulveda, California, studied thebrains of four people with narcolepsy who had died, andcompared them to normal brains.
Missing Neurons in Hypothalamus
The people with narcolepsy were missing neurons found inthe hypothalamus region of the brain that secrete hypocretin,Siegel reported in the journal Neuron.
“There are none to be seen — basically zero in thepatient,” Kitt said.
This tied in with findings by Dr. Emmanuel Mignot andcolleagues at Stanford University, who in 1999 found that alack of hypocretin caused narcolepsy in dogs, and who reportedtoday they had confirmed it causes narcolepsy in people.
They also found the hypocretin-producing cells were missingin human patients.
“We think that there’s something that specifically killsthe cells that make hypocretin. We don’t know how or why, butit’s most likely an autoimmune disease,” said Mignot, whoreported the findings in the journal Nature Medicine.
Cells Attack Healthy Tissue
Siegel and Kitt agreed that an autoimmune disorder, inwhich the body’s immune cells mistakenly attack healthy tissue,may be to blame.
“Narcolepsy can have an onset in adolescence and certainlythe early 20s and 30s, which is similar to other autoimmunediseases like multiple sclerosis,” Kitt said.
But Siegel also said it could be those cells aresusceptible to certain toxins in the environment.
Hypocretin peptides, also known as orexins, were discoveredonly two years ago. They can stimulate appetite and feeding andregulate the state of arousal.
Kitt said it was not surprising that a loss of hypocretinwould disrupt sleep, because of its role in the brain.
That means misery for narcoleptics, many who cannot work asa result or get drivers’ licenses. “They have sudden attacks ofsleep. It also disrupts their nighttime sleeping,” she said.
“It affects concentration, irritability and the overallfeeling of well-being. They are not happy people.”
Besides amphetamines, only one drug is approved for thetreatment of narcolepsy — Cephalon Inc.’s (CEPH.O) Provigil,known generically as modafinil. Its mechanism of action is notunderstood.
Orphan Medical Inc. (ORPH.O) plans to ask for U.S. Food andDrug Administration approval of its drug Xyrem for narcolepsy.The drug is GHB, or gamma hydroxybutyrate, which was banned in1991 after being widely abused as a “date rape” drug because itcould make people fall into a deep sleep.
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