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Sep 20, 2012
 |  BC Innovations  |  Targets & Mechanisms

ASIRTaining a Parkinson's disease target

A Tufts University team has compelling evidence that reducing sirtuin 2

activity could be beneficial in Parkinson's disease.1 The findings argue for developing brain-penetrating sirtuin 2 inhibitors.

Sirtuin 2 (SIRT2) is one of seven human sirtuins, a class of protein deacetylases with diverse roles in metabolic, inflammatory and autoimmune diseases. The best-studied member of the class is SIRT1, which first emerged in the 2000s when Harvard Medical School researchers showed that overexpressing or activating the target promoted disease resistance in multiple preclinical models of metabolic and neurological diseases.2

Based on those findings, Sirtris Pharmaceuticals Inc. was founded in 2004 to develop small molecule activators of sirtuins. The company was acquired by GlaxoSmithKline plc in 2008 for $651 million.

Since then, sirtuin activators have encountered roadblocks. In 2010, GSK discontinued development of Sirtris' lead compound, SRT510, and trials of next-generation SIRT1 activators in a range of metabolic and inflammatory conditions have not advanced beyond Phase II testing.

SRT2104, the most advanced next-generation SIRT1 activator, completed Phase I/II trials for type 2 diabetes, but GSK said it is no longer pursuing that indication with the compound. SRT2104 remains in Phase IIa development for ulcerative colitis (UC).

Although efforts to activate sirtuins in peripheral diseases have thus far yielded little...

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