Glaxo customized "red wine" drug potent in mice

LONDON Tue Nov 4, 2008 2:02pm EST

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LONDON (Reuters) - A drug in development that mimics a health-boosting compound found in red wine may be a powerful weapon in the fight against obesity and diabetes, researchers said on Tuesday.

A study of mice showed that the GlaxoSmithKline drug SRT1720 was about a thousand times more potent than resveratrol in activating an enzyme that helped the animals burn more energy and lower their insulin and glucose levels.

Mice fed a high-fat diet were tricked into switching their metabolisms to a fat-burning mode that normally takes over when energy levels are low, researchers reported in the journal Cell Metabolism.

"We are activating the same enzymes that are activated when people go to the gym," said Peter Elliott, a vice president at Sirtris Pharmaceuticals, the Glaxo unit that developed the drug. "That is why we believe the profile for this drug is very safe."

Resveratrol is found in abundance in grapes and in red wine and is believed to provide a number of health benefits, including preventing heart disease. An earlier study from the same team showed it lowered glucose and insulin in diabetics.

The natural compound has also drawn a lot of interest from scientists and some companies, including Glaxo, which this year paid $720 million for Sirtris in a deal that allowed them to acquire a number of developmental drugs for a range of diseases.

A Phase I trial has shown the treatment is safe and well-tolerated and the company plans to begin a wider Phase II trial with diabetics in 2009, added Elliott, who led on the study.

"Resveratrol makes mice live longer and stay healthier," said in a telephone interview. "This molecule does the same thing, but it is 1,000 times more potent so you don't need as much."

In type 2 diabetes, the body gradually loses the ability to use insulin properly to convert food to energy. Sugar levels shoot up, which can damage the eyes and kidneys, and cause heart disease, stroke and limb amputations.

The condition affects an estimated 246 million adults worldwide and accounts for 6 percent of all global deaths. Type 2 diabetes accounts for about 90 percent of all diabetes cases and is closely linked to obesity and physical inactivity.

Very strict diet and vigorous, regular and sustained exercise can reverse type 2 diabetes, but can be difficult for many people. Several different classes of drugs are on the market for type 2 diabetes.

In their study of diabetic mice, the researchers found that the experimental drug helped lower blood sugar and insulin levels to normal levels in just a few weeks with no harmful side effects.

It also lowered cholesterol and helped the mice on the drug lose a modest amount of weight compared to animals given a placebo, Elliott said. The mice on the drug were also able to exercise twice as long.

(Reporting by Michael Kahn, Editing by David Cowell)

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