Friday, December 3, 2010

Glaxo pulls the plug on resveratrol drug: end of the line?

Resveratrol, the antioxidant molecule from red wine (along with miniscule amounts from some berries and the non-edible parts of the peanut plant), took the world by storm a few years back when it was announced that it could trigger a specific metabolic change associated with significant lifespan extension. Though the phenomenon was only found at first in some strains of yeast under certain conditions, it was believed to work by activating an enzyme system known as sirtuins, which in turn control the switching on and off of genes associated with longevity and a range of diseases of aging. The potential for resveratrol-based compounds caught the attention of pharma giant GlaxoSmithKline, which acquired the rights to it for US $720 million in 2008. But this week Glaxo announced the suspension of all development of their product, known as SRT501, citing concerns about complications in a clinical trial for the blood cancer multiple myeloma. Many now wonder whether resveratrol has gone from darling to dud in only 2 short years.


Meanwhile, sales of resveratrol supplements, based on the naturally occurring and non-patentable molecule, have soared in recent years. Purveyors openly tout it as a “fountain of youth in a pill” and a miracle weight loss solution. Some advocates of natural healing are openly celebrating Glaxo’s failure, accusing them of greedily hijacking a perfectly good natural cure in the name of corporate greed by developing synthetic (and patentable) variations. Pfizer and Amgen have both weighed in recently with scientific publications casting doubt on the ability of resveratrol and its derivatives to activate sirtuins at all, pointing to evidence that the testing method was an artifact leading to false positive results. Is this the end of the road for resveratrol?

There’s support for both arguments, but don’t mark your calendars just yet for resveratrol’s funeral. For one, the natural molecule has a wide range of interesting capabilities, at least in lab studies. Clinical trials are ongoing and much remains to be learned about whether this translates to verifiable benefits in humans. (One thing that appears unlikely is the lifespan extension phenomenon via sirtuin activation, as it has not been found in mammals.) Glaxo was careful to point out that other resveratrol derivatives are being studied, and the point of synthesizing variations on the molecule is to find more potent versions with specifically targeted actions. (See the full quote below.) And without the prospect of return on investment, there is little funding available for studying the natural version. Until more results are in, my suggestion is to bear in mind that the whole thing started with red wine, which does confer longer life on average for moderate regular consumers, along with higher quality of life.

From Glaxo: ”We are focusing our efforts now on more selective SIRT1 activator compounds that have no chemical relationship to SRT501 and more favorable drug-like properties. Currently we have two of these latest generation compounds (SRT2104 and SRT2379) in several exploratory clinical trials.”

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