- The Washington Times - Monday, January 29, 2007


Researchers studying a condition that causes people to suddenly drop off to sleep are trying to turn what they have learned into a new way to help insomniacs get some shut-eye.

They found that blocking brain receptors for orexin, a blood peptide, promoted sleep in rats, dogs and people, according to a paper in yesterday’s online issue of the journal Nature Medicine.

Orexin, also known as hypocretin, is important in maintaining wakefulness. It is absent in the brains of people who suffer from narcolepsy, a chronic disorder in which people cannot regulate sleep-wake cycles normally. It is estimated to affect more than 135,000 people in the United States, according to the National Institutes of Health.

The researchers, led by Francois Jenck of the Swiss drug company Actelion Pharmaceuticals, reasoned that they might be able to induce sleep if they could block orexin.

They developed a drug that can block the receptors in the brain that respond to orexin-hypocretin. The researchers reported successful testing in rodents, dogs and men.

The first tests were proof of the concept, and the drug is being evaluated to establish the correct dosage, said Roland Haefeli, an Actelion spokesman. Researchers hope to decide this year whether to conduct a Phase 3 study, a detailed assessment of the drug that would be the final step before seeking U.S. government approval for its use. Such studies can take a few years.

Dr. Thomas Scammell, an assistant professor of neurology at Harvard University, said the work was “promising, with a certain amount of caution.”

“I think it may be the beginning of something quite exciting,” said Dr. Scammell, who was not part of the research team.

The drug works differently from other sleep aids, and the researchers “provide this very broad perspective, all the way from rodents to humans,” he said.

Dr. Scammell said the drug may work for people who cannot tolerate current sleeping pills well. But he said there are concerns that blocking orexin could cause a problem in the brain that is similar to narcolepsy.

“Subsequent studies will be important to make sure sleep quality is good,” he said.

Luis de Lecea, an associate professor of psychiatry and behavioral sciences at Stanford University, also sees promise in the research.

“This new compound may give rise to a new family of sleep aids,” Mr. de Lecea said. The advantage of targeting orexin-hypocretin, he said, is that it involves a relatively small number of neurons. Therefore, the new drug can be much more selective than current sleep-aid drugs.

But Mr. de Lecea, who was not part of the research team, cautioned that because of the way the study was done, it was impossible to determine the sleep quality.

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