Posted on 05/05/2009 9:51:29 AM PDT by neverdem
Mystery disease. Scientists monitor a narcoleptic patient.
Credit: Donna E. Natale Planas/Miami Herald/MCT/Newscom
The millions of people who suffer from narcolepsy might have their immune system to blame. Researchers have tied the disabling sleep disorder to two immune system genes, suggesting that it's an autoimmune disease. The discovery may eventually lead to improved narcolepsy treatments.
Narcolepsy affects 1 in every 2000 people, making it about as common as multiple sclerosis. The disorder encompasses an odd constellation of symptoms, including overwhelming daytime drowsiness, uncontrollable sleep attacks, and cataplexy, a sudden loss of muscle tone after an intense emotional outburst, like a good laugh. Sufferers rely on a mix of stimulants and sleep-suppressing drugs to control the disorder, but no cure exists.
Emmanuel Mignot, a sleep researcher with the Stanford University School of Medicine in Palo Alto, California, has been studying narcolepsy for more than 20 years. In the late 1990s, his team discovered that narcoleptics lack hypocretin, a hormone produced by a few brain cells that helps keep people and animals awake. In narcoleptic patients, the mechanism that makes the hormone is intact, but the cells are missing, suggesting that something destroys them.
Narcoleptics are also likely to have a specific variant of the human leukocyte antigen. HLA instigates the body's immune response by presenting fragments from pathogens to the immune cells, which in turn fight the pathogens off. Most autoimmune diseases, such as multiple sclerosis and type 1 diabetes, are associated with specific HLAs. Although later studies found no further evidence of an immune link, the coincidence made Mignot and many other sleep researchers suspect that an autoimmune attack was ravaging narcoleptics' hypocretin-producing cells.
To test the idea, Mignot teamed with Stanford geneticist Joachim Hallmayer and a network of colleagues spanning three continents. The researchers analyzed DNA from nearly 4000 participants, all of whom shared the same narcolepsy-linked HLA but only about half of whom had narcolepsy. They found that the narcoleptics in the study shared a version of another gene that tells T cells--the immune cells that destroy intruders--how to react to the pathogens that HLA molecules bring them. The result indicates that T cells and HLA, which together regulate much of the body's immune response, gang up in a unique way to destroy narcoleptics' hypocretin cells, the team reports online this week in Nature Genetics.
The study doesn't explain why T cells target the hypocretin cells specifically, says Mignot. It also sheds no light on what triggers the attack in the first place, a mystery for most autoimmune diseases. "We don't know why bodies go haywire and start attacking themselves," he says. But Mignot hopes future studies will reveal the culprit. In the meantime, knowing the autoimmune trigger could lead to new and more effective treatments for narcolepsy, he says.
"We've known for years that narcolepsy is probably an autoimmune disease, but every attempt to prove it has turned up nothing," says Michael Silber, a neuroscientist with the Mayo Clinic in Rochester, Minnesota. "This study doesn't conclusively prove narcolepsy is autoimmune, but it's a major step in that direction."
speaking of narcolepsy
“The details of my life are quite inconsequential.... Very well, where do I begin? My father was a relentlessly self-improving boulangerie owner from Belgium with low-grade narcolepsy and a penchant for buggery. My mother was a 15-year-old French prostitute named Chloe with webbed feet. My father would womanize; he would drink. He would make outrageous claims like he invented the question mark. Sometimes, he would accuse chestnuts of being lazy. The sort of general malaise that only the genius possess and the insane lament... My childhood was typical: summers in Rangoon... luge lessons... In the spring, we’d make meat helmets... When I was insolent I was placed in a burlap bag and beaten with reeds pretty standard, really. At the age of 12, I received my first scribe. At the age of 14, a Zoroastrian named Vilmer ritualistically shaved my testicles there really is nothing like a shorn scrotum it’s breathtaking... I suggest you try it.” - Dr Evil
FReepmail me if you want on or off the diabetes ping list.
What’s that supposed to mean?
It’s humor!
Dr. Evil from the Austin Powers movies.
Interesting area of NeuroBio Science
The results of undiagnosed Sleep Apena can
also mimic Narcolepsy.
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