Can drugs that supposedly “activate” a controversial target—sirtuin proteins—stop or even reverse the aging process? A new report this week said “No.” According to this report, published Wednesday night in Nature, sirtuin activators do not extend lifespan in roundworms and flies and earlier studies that said they did were flawed. Nonetheless, GlaxoSmithKline (GSK) continues to invest hundreds of millions of dollars into developing drugs to hit these targets—more about their findings below—and if the drugs work, for whatever reason, the scientific squabbles will not matter.

I recently had the chance to hear Harvard professor David Sinclair talk publicly about his and GSK’s research into sirtuin activators. Sinclair was the scientific founder of Sirtris and he reported at a forum on longevity in Cambridge, MA, that GSK has high hopes of near-term confirmation in mice that some sirtuin activators do extend lifespan. Based on its continued investment, GSK still believes that the $720 million acquisition of Sirtris in 2008 was a smart one.

The Nature report, just the latest in a series of publications that question the sirtuin-longevity link, will be even tougher for Sinclair and other sirtuin researchers to overcome. The new research reported that sirtuin proteins, when overexpressed in nematode worms and fruit flies, do not actually have an effect on longevity. This directly contradicts the original publications linking Sir2 and other sirtuins with increased lifespan. The new report further goes on to contradict the landmark 2006 paper, also published in Nature, in which Harvard researchers led by Sinclair reported that mice fed resveratrol which, they demonstrated using expression analysis, activated sirtuins, live on average 20 percent longer and in some cases much longer than that.

The same researchers, both at University College London, went on the record as sirtuin skeptics in 2007. David Gems and Linda Partridge then set out to prove their claim that the original sirtuin and resveratrol findings, which led to the founding and eventual acquisition of Sirtris, were irreparably flawed. Building on earlier reports that the round worms used in the original studies carried a gene that control organisms did not carry, and that it was this gene that predisposed the worms to live longer, Gems and Partridge showed in this paper that organisms identical to one another except for the expression level of sirtuins could not be made to live longer.

Sirtuin research is nothing if not contentious. Apparently eager to fan the flames, Nature in the same issue this week published a rebuttal from Leonard Guarente, the author … Next Page »

Comments (2) | Reprints | Share:          

There’s bad news this week about one of the much-hyped drug candidates based on the red wine chemical called resveratrol. Several news outlets are reporting that safety concerns have prompted GlaxoSmithKline to halt a mid-stage clinical trial of the drug, called SRT501, which the London-based drug giant gained in its $720 million buyout of Sirtris Pharmaceuticals in 2008.

Glaxo put a stop to a Phase II trial of the drug in patients with multiple myeloma, a cancer of the bone marrow and plasma, after some patients in the study developed a condition that can lead to kidney failure, according to the Wall Street Journal. Some of the patients in the trial were also taking bortezomib, an approved cancer drug marked as Velcade. The chemist Derek Lowe broke this news on his blog, “In the Pipeline,” on Monday based on an April 22 update on the trial posted on ClinicalTrials.gov, a U.S.-government-run registry of clinical trials.

Normally, the failure of a mid-stage trial at a big pharmaceutical company wouldn’t generate tons of press coverage, but this study is different—perhaps because we reporters have heaped so much coverage on Sirtris, resveratrol, and related “anti-aging” drugs in the first place. (Resveratrol and drugs candidates like SRT501 that are based on it are believed to activate anti-aging enzymes called sirtuins.)

Despite the concerns in Glaxo’s multiple myeloma trial, Sirtris’s formulation of resveratrol had previously been studied in patients with diabetes and other cancers without the same safety problems. Also, Sirtris, which now operates as a subsidiary of Glaxo, says that it has discovered new compounds that are vastly more potent than resveratrol and SRT501, and one such new compound has become the focus of its efforts to find new ways to treat diabetes. Still, the ill-fated study of SRT501 in multiple myeloma is one reason to remain skeptical of the health benefits of resveratrol until they can be proven in further human studies.

Comments (6) | Reprints | Share:          

A who’s who of the Boston-area life sciences scene (including MIT Institute Professors Robert Langer and Philip Sharp) turned out at Harvard Medical School yesterday for the first Boston Biotech R&D Conference. It was a good place to be for anyone aiming to network with biotech-focused venture capitalists, fund managers, executives, academic luminaries, and industry officials.

At my makeshift office on a seat outside one of the meeting rooms, I could feel the pulse of the local life sciences sector from the banter. Much of it about the hurt put on biotechs due to the stormy financial climate. “It’s a great time to have a portfolio full of illiquid assets,” said one venture capitalist (whom I won’t name because he didn’t know that he had an eavesdropping reporter sitting behind him). I also chatted with Christoph Westphal, CEO of Sirtris, the Cambridge, MA-based biotech firm. Westphal, one of the chief organizers of the event, said the mood was surprisingly optimistic at the conference, despite the financial crisis.

“The economic meltdown hasn’t affected all the great science that’s going on, all it has done is worked its way into the system where it’s harder to bring money into companies,” Westphal said. “My overall view is that this is a more optimistic and positive meeting than I could have hoped for and I think it’s because we’re doing it at Harvard Medical School instead of in New York or in a financial setting.”

There were certainly lighter moments. During a session with a panel of fund managers and analysts focused on life sciences investments, someone from the audience asked the panelists which of the candidates for U.S. President would be best for the life sciences industry. Most of the panelists didn’t think it mattered, yet investment analyst Andrea Bici of London-based Schroder Investment Management told the audience that Sen. John McCain’s more favorable tax policy for large corporations would leave large drug companies with more capital for R&D purposes.

David Sinclair, the scientific co-founder of Sirtris and a professor at Harvard Medical School, gave a tutorial on his discovery of drugs to treat diseases of aging called “Finding Anti-Aging Drugs for Dummies.” In talking about the ability of Sirtris’ drugs to mimic calorie restriction, he noted that he once met a set of people who try to get the same benefits from actually eating less. “I’ve met these people,” he said, “and they’re perpetually hungry.” He even acknowledged that he tried their diet but gave it up after a week because he was so hungry. Good thing his company’s drugs have the potential to let people eat normally while their cells act as though were dieting.

Comments | Reprints | Share: