Thursday, March 28, 2013
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Sirtuin 1 (SIRT1)
In vitro studies identified a SIRT1 mutation that could be
associated with type 1 diabetes. Genotyping and sequencing identified a
leucine to proline substitution at residue 107 of SIRT1 in four family members
with type 1 diabetes and one with ulcerative colitis (UC). In b
cells, expression of the mutant SIRT1 disrupted normal SIRT1 activity
and increased production of cytokines, chemokines and nitric oxide compared
with expression of wild-type SIRT1. In myoblasts isolated from healthy
controls, transduction with the SIRT1 mutant caused insulin resistance. Next
steps include developing SIRT1 activators to treat type 1 diabetes.
Elixir Pharmaceuticals Inc.'s
EX-527, an oral SIRT1
inhibitor, is in Phase II testing to treat Huntington's disease (HD).
GlaxoSmithKline plc's GSK2245840 SIRT1 activator
is in Phase II testing to treat psoriasis. The compound completed Phase I/II
trials for type 2 diabetes, but the pharma said it is no longer pursuing that
indication with the compound.
Ildong Pharmaceutical Co. Ltd.'s
SIRT1 activator, ID2244, is in preclinical
development to treat metabolic syndrome.
Published online March 28, 2013
Patent and licensing status
Biason-Lauber, A. et al.
Cell Metab.; published online March 5, 2013;
Contact: Marc Y. Donath, University Hospital Basel, Basel,
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