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Researchers seek way to help insomniacs get some shut-eye

Associated Press

WASHINGTON — Researchers studying a disease 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 Sunday'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 research team, 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 now being evaluated to establish the correct dosage, said Roland Haefli, an Actelion spokesman. Researchers hope to decide this year whether to conduct a phase-three 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.

Narcolepsy victims often also experience cataplexy, a condition in which they lose control of muscle tone for a few seconds to minutes. Dr. Jenck said in a telephone interview that the drug tests did not prompt indications of cataplexy.

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 that are available and the researchers “provide this very broad perspective, all the way from rodents to humans,” he said in a telephone interview.

Dr. Scammell said the drug may work for people who do not 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. Also, cataplexy is difficult to study in the lab because it is often triggered by strong emotions, he said.

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

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

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

Dr. Jenck's research was funded by Actelion.

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