Longevity Pill Tested in Humans - resveratrol
What if I told you there was a pill that slows aging and allows you to live a healthy life to age 100?
Such a pill may exist right now. It’s being tested in people in very early-stage human clinical trials. Today, the company making the pill, Sirtris Pharmaceuticals, announced its findings from preclinical testing in cells and animals, and also from tests conducted on 85 male volunteers this summer.
The verdict: so far, the pill works, although it will be years before we know how well it works, or if it can actually extend the life span of people in the same way that it has bumped up the life span of mice.
Speaking today at the Annual Metabolic Diseases Drug Discovery and Development World Summit in San Diego, Sirtris’s senior director of biology, Jill Milne, announced that the drug, SRT501, reduces glucose and improves insulin sensitivity in animal and in vitro studies of the drug’s effect on type 2 diabetes. In people, the drug was tested for dose, safety, tolerability, and pharmacokinetics–that is, how well the drug was absorbed, distributed, metabolized, and removed from the body.
Phase 1b trials are already under way to test safety and pharmacokinetics on patients with type 2 diabetes. Later-phase trials will test to see if the drug actually works in diabetics.
SRT501 is a proprietary chemical developed by Sirtris that’s based on the naturally occurring resveratrol that company cofounder David Sinclair of Harvard University has been studying for its effects in extending life span in a number of organisms, including yeast, flies, and mice. Last year, Sinclair created a sensation when he published a paper in Nature detailing how mice on a high-fat diet that were fed large doses of resveratrol were as healthy as mice on a regular diet. Resveratrol also sharply extended life span, produced positive changes in insulin sensitivity and other diabetes-preventing mechanisms, and increased energy production in cells. The mice were given very high doses of resveratrol–22 milligrams per kilogram of weight. In comparison, a liter of red wine delivers 1.5 to 3 milligrams. To match the results in the mice, a 150-pound human would need to drink 750 to 1,500 bottles of wine a day.
Sinclair says that SRT501 is a thousand times more potent than naturally occurring resveratrol, which gives it the same punch as the resveratrol in all those bottles of wine.
Sinclair believes that resveratrol activates a gene called SIRT-1, which is associated with the regulation of life span in several animals. This contention is disputed by some critics: they argue that the mechanism by which resveratrol works is still poorly understood.
Because humans are so long-lived, SRT501 can’t be easily tested for longevity in humans–nor does the Food and Drug Administration recognize “increased life span” as an allowable indication for an approved drug. This is why Sirtris is testing SRT501 for diseases related to aging, such as type 2 diabetes. However, should the drug be approved for diabetes, it will undoubtedly be used to extend life span by many people without diabetes.
The drug still has years of testing to go and faces many hurdles. It may not work. But if it does, the consequences will be profound. For instance, it will mean that more people will be alive on the earth. Age 90 will be the new 70, and 70 the new 50, with profound impacts on everything from social security to retirement age. It may also mean fewer people with diabetes, Alzheimer’s, and some cancers.
Can one pill do and cause all that? Critics have long said no–that such a compound will not work in humans. But they also said it wouldn’t work in mice–until it did work. (At least in fat mice.)
So let’s sip some pinot noir and wait for more results from Sirtris. After all, we’re not getting any younger.
Look for my profile of longevity researcher David Sinclair in the September/October issue of Technology Review.
CAMBRIDGE, Mass.–(BUSINESS WIRE)–July 17, 2007–Sirtris Pharmaceuticals, Inc. (NASDAQ: SIRT), a biopharmaceutical company focused on discovering and developing small molecule drugs to treat diseases of aging, announced today that it presented data from pre-clinical and Phase 1a studies at the 6th Annual Metabolic Diseases Drug Discovery and Development World Summit in San Diego, California on July 17, 2007. As previously announced, Jill Milne, Ph.D., Senior Director of Biology at Sirtris, delivered a keynote address “SIRT1 Activation: A Novel Mechanism for Treating Type 2 Diabetes.”
Dr. Milne presented data which showed that SRT501, Sirtris’ proprietary formulation of resveratrol, reduces glucose and improves insulin sensitivity in multiple pre-clinical models of Type 2 Diabetes. Dr. Milne also presented pharmacokinetic (PK) data from a Phase 1a study conducted by Sirtris in which healthy volunteers who were dosed with SRT501 had an improved exposure as compared with other published studies. Both the area under the curve concentrations (AUC) as well as the maximal concentrations (Cmax) were shown to be improved with SRT501 as compared with literature values for resveratrol. SRT501 is currently being tested in a Phase 1b study in patients with Type 2 Diabetes.
Furthermore, Dr. Milne presented data with certain Sirtris proprietary novel chemical SIRT1 activators, structurally unrelated to resveratrol, which were shown to reduce glucose, improve insulin sensitivity, improve glucose tolerance, and increase the number and function of mitochondria in multiple pre-clinical models of Type 2 Diabetes. In addition, studies in a pre-clinical model demonstrate improved insulin sensitivity in muscle, liver, and fat cells.
“Sirtris scientists continue to make significant progress in the development of SIRT1 activators for diseases of aging such as Type 2 Diabetes. Indeed, the new data presented today further extend Sirtris’ scientific leadership in advancing sirtuin modulators as a new class of innovative therapeutics,” said Christoph Westphal, M.D., Ph.D., Chief Executive Officer of Sirtris.
About Sirtris Pharmaceuticals
Sirtris Pharmaceuticals is a biopharmaceutical company focused on discovering and developing proprietary, orally available, small molecule drugs with the potential to treat diseases associated with aging, including metabolic diseases such as Type 2 Diabetes. Our drug candidates are designed to mimic certain beneficial health effects of calorie restriction, without requiring a change in eating habits, by activation of sirtuins, a recently discovered class of enzymes that control the aging process. The company’s headquarters are in Cambridge, Massachusetts.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, the progress of pre-clinical and clinical studies of SIRT1 activators, the results of pre-clinical studies as compared with other published studies, Sirtris’ position in the sirtuin field, and the potential for sirtuin modulators to receive regulatory approval. These forward-looking statements about future expectations, plans and prospects of Sirtris Pharmaceuticals involve significant risks, uncertainties and assumptions, including risks related to the lack of results that would provide a basis for predicting whether any of the Company’s product candidates will be safe or effective, or receive regulatory approval, the possibility that results of pre-clinical studies are not necessarily predictive of clinical trial results, the Company’s potential inability to initiate and complete pre-clinical studies and clinical trials for its product candidates, the fact that none of the Company’s product candidates has received regulatory approvals, the potential inability of the Company to gain market acceptance of the Company’s product candidates, and those other risks factors that can be found in the Company’s filings with the Securities and Exchange Commission. Actual results may differ materially from those Sirtris Pharmaceuticals contemplated by these forward-looking statements. Sirtris Pharmaceuticals does not undertake to update any of these forward-looking statements to reflect a change in its views or events or circumstances that occur after the date of this release.
CONTACT: Investor Contact:
Sirtris Pharmaceuticals, Inc.
Michelle Dipp, M.D., Ph.D., 617-252-6920
or
Media Contact:
Pure Communications
Sheryl Seapy, 949-608-0841
SOURCE: Sirtris Pharmaceuticals, Inc.
by Mooney