Pharma giant GlaxoSmithKline has suspended a small clinical trial of SRT501, a proprietary form of resveratrol, on safety concerns. Sirtris Pharmaceuticals, which U.K.-based GlaxoSmithKline bought for $720 million in 2008, is developing the drug.
Sirtris has been testing SRT501 and others in several diseases, such as diabetes and cancer, hoping they may provide health benefits by activating enzymes in the body called sirtuins. One sirtuin, SIRT1, has demonstrated anti-aging properties in yeast. But different SIRT1 studies since have yielded inconsistent results on that front.
Advertisement"The primary purpose of this study is to determine the safety and tolerability of SRT501 (5.0 g) with or without concurrent bortezomib administration, when administered once daily in 21 day cycles, in male and female subjects with Multiple Myeloma," according to the National Institutes of Health's ClinicalTrials site.
Bortezomib (INN, originally codenamed PS-341; marketed as Velcade by Millennium Pharmaceuticals) is the first therapeutic proteasome inhibitor to be tested in humans. It is approved in the U.S. for treating relapsed multiple myeloma and mantle cell lymphoma. In multiple myeloma, complete clinical responses have been obtained in patients with otherwise refractory or rapidly advancing disease.
Some of the patients in the Glaxo trials developed cast nephropathy, a complication of multiple myeloma that causes kidney disease. The company isn't yet certain of the cast nephropathy's cause and hasn't seen this event in past SRT501 trials, says GlaxoSmithKline spokeswoman Sarah Alspach.
"New patient enrollment was put on hold while we analyze the data that was collected to date," according to a company statement. "Investigators and regulators in the U.K. and Denmark were appropriately notified of the decision to temporarily hold further enrollment while determining the next step for this particular trial."
Some current patients have opted to continue with the study after being informed of the development, notes Alspach.
GlaxoSmithKline is now focusing its efforts on more potent and selective SIRT1 activators -- SRT2104 and SRT2379 -- both of which are involved in several exploratory clinical trials.
Even if resveratrol and the Sirtris compounds don't combat ageing, this doesn't make them worthless - far from it, some experts opine, wrote Ewen Callaway in New Scientist in January last.
It is already known that high doses of resveratrol can limit the toll of a high-fat diet on mice, although the compound doesn't seem to extend the lifespan of healthy rodents. "It may be that resveratrol-like compounds are going to be therapeutically useful in people," says Matt Kaeberlein, a biochemist at the University of Washington in Seattle.
If they aren't, Kaeberlein worries that enthusiasm and investment in longevity-boosting drugs could dry up. That would be a shame, he says, given the promise of another age-hacking drug: rapamycin.
Last year, a group led by David Harrison at the Jackson Laboratory in Bar Harbor, Maine, revealed that aged mice given rapamycin, a transplant drug
Rapamycin, Harrison says, blocks a pathway called TOR that responds to nutrients in the environment which may be fundamental to ageing, and a furious search is under way to find chemicals that work in a similar way without dampening the immune system. "Right now everybody and his uncle are trying to find something that acts like rapamycin."