Mid-afternoon sluggishness plagues just about everyone, but for narcoleptics, every day is a struggle to stay awake. Now two studies show that the brains of people with narcolepsy are missing a key protein, as well as the neurons that are supposed to produce it--suggesting that replacing the protein might treat the disease.
Narcolepsy leaves sufferers sleepy and prone to sudden collapses, often brought on by heightened emotions. About 1 in 2000 people suffer from the condition. Sleep researchers working on a breed of dogs that has narcolepsy-like symptoms knew that the animals don't properly use a protein called hypocretin, also known as orexin. Two research teams looked at the brains of people who had suffered from narcolepsy for signs of hypocretin troubles.
One team, led by Emmanuel Mignot of Stanford University, found that people with narcolepsy don't seem to make hypocretin at all. The researchers found no sign of the protein in six brains of deceased people who'd had narcolepsy, they report in the September issue of Nature Medicine. They suspect that errant immune cells destroy the neurons that should pump out hypocretin--a theory based in part on previous research showing that human narcoleptics carry a particular type of immune cell.
More support for this theory comes from neurobiologist Jerome Siegel of the VA Medical Center in Sepulveda, California, and the University of California, Los Angeles, and colleagues. After examining the brains of 16 cadavers, the team found scarring in the hypothalamus, where hypocretin-producing cells should be concentrated. Only hypocretin-producing cells were destroyed; neighboring cells appeared undamaged. All told, the narcoleptic brains had barely 10% as many hypocretin-producing cells as normal brains, the team reports in the September issue of Neuron.
Currently, narcoleptics can take stimulants to relieve drowsiness, but replenishing patients' hypocretin might address the root cause. "This really provides a reasonable means for curing narcolepsy," says Masashi Yanagisawa of the University of Texas Southwestern Medical Center in Dallas.