Red Wine Drug Shows Proof That It Combats Aging

By Alexis Madrigal 01.08.08 | 12:00 AM

SAN FRANCISCO -- For the first time, scientists have proof in human subjects that a derivative of an ingredient in red wine combats some symptoms of aging. Sirtris Pharmaceuticals announced the results here on Monday at the JPMorgan Healthcare Conference.

Resveratol, naturally found in red wine, stimulates a gene known as SIRT1, which has been linked with extended lifespans in rodents. The new study is the first time similar effects have been replicated in humans.

"We believe that this is the first time that a drug candidate has shown efficacy in a disease of aging by targeting the genes that control aging," said Christoph Westphal, CEO of Sirtris.

Sirtris was co-founded by David Sinclair, a Harvard Medical School researcher, who discovered SIRT1's role in regulating lifespan. His early work was in yeast, and he later showed that stimulating SIRT1 through a calorie-restricted diet helped animals live longer. Then, Sinclair found resveratol, which stimulates the same gene with results similar to calorie-restriction but without the diet. Resveratrol's effects in mice touched off a storm of excitement among people, including Sinclair, who began taking the drug in its over-the-counter form hoping to extend their lifespans.

Sirtris' proprietary formulation of the drug significantly reduced blood sugar in 67 diabetic patients as compared with a placebo group. The results are an important milestone in bringing resveratrol-related drugs to market.

The study, however, ran just 28 days and had conservative goals: to measure whether a resveratol formulation called SRT501, which is five times easier for the body to use than naturally occurring resveratol, was safe and had some activity in humans. Getting the drug through the regulatory process will take until at least 2012, the company said.

The results partially answer skeptics like Steven Austad, a cellular biologist and longevity researcher at the University of Texas, who expressed doubts about the impact of resveratol in humans to Wired News last year after mouse studies showed longevity gains.

"People in the research community tend to think of mice as small little furry humans with long tails, but they're not," Austad said at the time. "We don't know what it will do."

Sirtris can now say it does know what SRT501 does, at least for a small number of patients over a short period of time: It works.

Patients in the trial were given 2,500 or 5,000 milligrams of the drug in liquid form. Both groups had positive outcomes with no side effects. Westphal said during a question-and-answer session following his presentation at the JP Morgan Healthcare Conference that the unusually high doses were necessary because resveratrol is not a very potent molecule.

That's why the company is also working with other molecules -- potential drugs -- that are unrelated to resveratrol but also stimulate the SIRT1 gene. Some of the molecules could be up to 1,000 times more potent than resveratrol, he added.

Still, SRT501 was effective enough that Sirtris is continuing to push the drug through clinical trials.

"Based on the positive results, and the fact that there are a lot of desirable characteristics to SRT501, we've initiated a Phase IIa study combining SRT501 with the most common diabetic drug, metformin," said Westphal. "Those data are back in the second half of this year."

Sirtris had an initial public offering of its stock back in May of 2007 and is up 23 percent since that time. Following the clinical trial announcement, the stock gained 1.5 percent in after-hours trading.