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Parkinson's disease (PD)

Sirtuin 2 (SIRT2)

Mouse studies suggest antagonizing SIRT2 could be useful for treating PD. In a mouse model of dopaminergic neurotoxin-induced PD, Sirt2 knockout led to lower levels of neuronal apoptosis than normal Sirt2 expression. Next steps include testing the effect of Sirt2 deletion in other mouse models of PD and developing selective, brain-penetrant SIRT2 inhibitors.
Indus Biotech Pte. Ltd. has the SIRT2 inhibitors INDUS815B and INDUS815C in preclinical development for PD and Huntington's disease (HD), respectively. Elixir Pharmaceuticals Inc. and Siena Biotech S.p.A. have selisistat (EX-527), an inhibitor of the related enzyme SIRT1, in Phase I testing for HD. (see ASIRTaining a Parkinson's disease target, page 6)

SciBX 5(37); doi:10.1038/scibx.2012.985
Published online Sept. 20, 2012

Unpatented; licensing status not applicable

Lui, L. et al. J. Biol. Chem.;
published online Aug. 16, 2012;
Contact: Gizem Donmez,
Tufts University School of Medicine, Boston, Mass.