SIRT2 Inhibitors as Novel Therapeutics for Myocardial Infarction and Ischemic Stroke and to Prevent Necrosis

Sirtuin 2 (SIRT2) inhibitors to reduce necrosis and, thereby, as novel therapeutics to treat ischemic stroke and myocardial infarction. Accumulating evidence indicates that programmed necrosis plays a critical role in cell death during ischemia-reperfusion. NIH investigators have shown that the NAD-dependent deacetylase SIRT2 binds constitutively to receptor-interacting protein 3 (RIP3) and that deletion or knockdown of SIRT2 prevents formation of the RIP1-RIP3 complex in mice. These investigators also found that genetic or pharmacological inhibition of SIRT2 blocks cellular necrosis induced by TNF-alpha and RIP1 is a critical target of SIRT2-dependent deacetylation. Further studies also showed that the hearts of Sirt2^–/– mice, or wild-type mice treated with a specific pharmacological inhibitor of SIRT2, show marked protection from ischemic injury. These results implicate SIRT2 as an important regulator of programmed necrosis and indicate that SIRT2 inhibitors may constitute a novel approach to protect against necrotic injuries, including ischemic stroke and myocardial infarction.

Potential Commercial Applications:		Competitive Advantages:
Novel therapeutics to protect against necrotic injuries. Novel therapeutics to treat ischemic stroke and myocardial infarction. Novel therapeutics to treat diseases in which necrosis is involved.		None of the currently available drugs address the necrotic damage caused due to ischemia and reperfusion. Using a Sirt2 inhibitor could limit the damage caused by necrosis and contribute to accelerated recovery in patients suffering from these conditions.

Development Stage:

• Early-stage
• Pre-clinical
• In vitro data available
• In vivo data available (animal)

Inventors:

Nisha Narayan (NHLBI)  ➽ more inventions...

Toren Finkel (NHLBI)  ➽ more inventions...


Intellectual Property:
US Application No. 61/723,496

Publications:
Narayan N, et al. PMID 23201684

Collaboration Opportunity:
The NHLBI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize retinoid-related orphan receptors (RORs) function in chronic diseases. For collaboration opportunities, please contact Ms. Peg Koelble at koelblep@mail.nih.gov or 301-594-4095.


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OTT Reference No: E-003-2013-0
Updated: May 9, 2018