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12:00 AM
May 05, 2008
 |  BioCentury  |  Strategy

GSK's SIRTainty

The planned $720 million cash acquisition of Sirtris Pharmaceuticals Inc. by GlaxoSmithKline plc extends the big biology land grabs of recent years to the field of sirtuins, a class of histone deacetylases with diverse but as-yet poorly understood roles in disease biology. The challenge now is to sort out which sirtuins are druggable targets, for what indications and in what manner.

The deal will combine GSK's own sirtuin drug discovery program with Sirtris' discovery platform, IP and next-generation compounds that improve on the biotech's initial clinical stage-candidate, SRT501. SRT501 is a formulation of the natural compound resveratrol whose reported mode of action has generated some debate in the academic literature.

Sirtuins first came to light as genetic regulators of senescence and aging in yeast, but mammalian homologs have since cropped up in preclinical studies as regulators of metabolic disease, cancer, inflammation and neurodegeneration. However, the specific roles of sirtuins in human diseases are still unclear.

"The jury is still out about whether sirtuins have any role in mammalian aging," said Torren Finkel, principal investigator at the NIH's National Heart, Lung and Blood Institute. Instead, he said, sirtuins are probably more important for regulating energy homeostasis and mitochondrial activity in mammals, so Sirtris' focus on metabolic disease is thus a likelier bet for therapeutics.

"Sirtuins are really central to metabolism, so it's not fortuitous that they affect diabetes," Finkel told BioCentury.

For proof of principle, Sirtris has moved SRT501 into Phase IIa trials for Type II diabetes and Phase I for MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), a rare hereditary disorder.

The compound is an agonist of sirtuin 1 (SIRT1), the human...

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