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Oct 20, 2016
 |  BC Innovations  |  Product R&D

Sirtuins forge ahead

How Forge Life Science is targeting sirtuins to treat viral infections

Since sirtuins hit the scene as modulators of numerous cellular pathways over 20 years ago, the enzymes have been implicated in metabolic diseases, aging and cancer. Now Forge Life Science LLC has licensed findings from Princeton University showing sirtuins have activity against a large number of viruses, and wants to create broad-spectrum antivirals that modulate sirtuins - analogous to the broad-spectrum antibiotics that revolutionized treatment of bacterial infections.

“There are roughly 115 different human viruses that have been sequenced and are known to cause disease in man, and we only have FDA-approved antivirals that can treat eight of them,” said Forge President and CEO Lillian Chiang. “If you add in vaccines, we can defend against only 15-20 viruses in a pandemic.”

She believes that modulating sirtuins will produce a more efficient treatment strategy than developing targeted therapies for each of the remaining viruses. The goal is to provide physicians with drugs that can be prescribed based on symptoms, rather than requiring timely and expensive diagnostic tests to identify the infectious agent.

Because sirtuins are targets on human immune cells rather than on viruses, Chiang believes Forge’s molecules are less likely to run into the problems of resistance that have arisen for some targeted antivirals and that are plaguing antibiotics.

Sirtuins constitute a family of seven enzymes with intracellular regulatory protein functions, including deacetylation. The most well known modulator is resveratrol, a natural compound found in red wine with anti-aging properties and metabolic benefits that indirectly activates SIRT1. Forge is designing small molecule sirtuin modulators that have a combination of activating and inhibitory activity across the seven different sirtuins, with the mode of action of each compound tailored to best treat viruses that infect different tissues.

In 2008, GlaxoSmithKline plc acquired Sirtris Pharmaceuticals Inc. and its sirtuin modulators, including SRT501, an orally bioavailable formulation of resveratrol. GSK discontinued development of SRT501 after data from a 2010 Phase IIa trial showed the compound had minimal efficacy and increased the risk of renal complications in patients with multiple myeloma (MM). GSK spokesperson Mary...

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