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Promising antiobesity drug fails to produce clinically meaningful weight loss

A drug designed to target a powerful hunger-stimulating factor that has long been considered a prime target for antiobesity therapy failed to produce clinically meaningful weight loss in obese people in a long-term clinical trial. People taking the drug known as MK-0557 for a year consistently lost about three pounds more than those taking a placebo, researchers reported in the October issue of the journal Cell Metabolism, published by Cell Press.

The results, which are the culmination of a 10 year program of study, suggest MK-0557 alone will not provide a useful weapon in the fight against obesity. The possibility remains, however, that the treatment could potentially play a role in future combination therapies, according to the research team that includes Steven Heymsfield and Ngozi Erondu of Merck & Co., Inc. Heymsfield said that combination therapies were among the possibilities being considered by scientists conducting obesity research.

"The current findings add to a growing sense that you will have to try a lot of different targets or get an even better understanding of the scientific underpinnings in order to unwire the food intake system with some combination of drugs," Heymsfield said. "Finding safe and effective antiobesity drugs is not unlike the challenge and complexity of sending the space shuttle into orbit."

MK-0557 blocks brain receptors that respond to the hunger factor called neuropeptide Y (NPY). NPY, whose role in driving appetite Heymsfield likens to an accelerator in a car, is one in a chain of players in the hunger pathway that includes the fat hormone leptin. Leptin hormone sends signals to the brain about the level of energy stores available, information that is then used to gauge metabolism and appetite.

Scientists discovered NPY more than two decades ago, making it one of the first identified appetite stimulants, but it was only after the discovery of leptin in 1994 that the neuropeptide's key role an
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Contact: Heidi Hardman
hhardman@cell.com
617-397-2879
Cell Press
3-Oct-2006


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