The research suggests that narcoleptics' overwhelming urge to fall asleep may result from a glitch in signals sent between cells in the hypothalamus, a part of the brain that regulates appetite and other basic drives.
Narcolepsy can cause a person to fall into deep sleep suddenly, without warning. The condition plagues 125,000 Americans, many of whom are not able to drive or hold a job because they could collapse at any moment. They are excessively sleepy during the day and, at times, remain conscious as their entire body goes limp and they find themselves unable to move.
A team of scientists at the Sleep Research Center at Stanford University studied Doberman pinschers and Labrador retrievers with narcolepsy.
The Stanford team traced the condition in these dogs to a gene that makes a receptor -- a bit of material on the surface of brain cells that allow them to get signals from other cells. This particular receptor receives messages that are transmitted by a protein called hypocretin-2.
Among the Dobermans, the defect is an extra piece of DNA that throws the rest of the gene out of alignment. Among the retrievers, a chunk of the DNA is missing. In both instances, the body's cells can no longer use the DNA to build hypocretin-2.
Because the gene is defective, it makes a receptor that fails to recognize hypocretin-2, so the signal never gets through.
"This work implicates hypocretin in sleep regulation, which gives us a wonderful new handle on how we might approach sleep control" with new medicines, said Dr. Charlotte McCutchen of the National Institute of Neurological Disorders and Stroke, which financed the research.
Instead of treating narcolepsy with stimulants such as amphetamines, which have unwanted side effects, she said, it soon may be possible to find drugs that work solely on the brain's hypocretin system. Medicines could be designed to both prevent sleep in narcoleptics and induce it in insomniacs.
One surprising aspect of the discovery, according to Benjamin Lewin, Cell's editor, is that the researchers of the second study discovered earlier that hypocretins play a role in controlling appetite.
Last year, Dr. Masashi Yanagisawa of the Howard Hughes Medical Institute in Dallas found that a protein dubbed orexin-B stimulates the appetite. Now it turns out that orexin-B and hypocretin-2 are the same thing.
To study the protein's effects on appetite, Yanagisawa produced gene-altered mice that cannot make hypocretin-2. The scientists hooked up infrared cameras to watch their eating habits at night, when they are most active.
"We saw this very bizarre change in behavior," Yanagisawa said. "The mice would be grooming, running and burrowing and then all of a sudden they wold fall over and stay there for one or two minutes."
His team's accidental finding has fueled interest in the mysterious link between appetite and narcolepsy, which the genetically altered mice suffered from.
But Juliette Faraco, a geneticist who co-authored the Stanford study, cautioned that the cause of human narcolepsy may turn out to be a bit more complicated, and involve more than the gene identified in the new experiments.
In identical twins, she said, one may suffer from narcolepsy while the other does not. "That means there need to be environmental triggers" that spark the appearance of the condition.
"But now we have so much more information about where to look in humans," she said.