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A New Approach to Boosting Good Cholesterol

Activating longevity-linked genes could protect against atherosclerosis.
October 12, 2007

Hoping to repeat the blockbuster success of cholesterol-lowering statins, pharmaceutical companies have been doggedly searching for a new kind of cholesterol drug–one that pumps up levels of heart-healthy good cholesterol. High levels of bad cholesterol (LDL) build up in the arteries and lead to heart attacks, while good cholesterol (HDL) appears to protect against cardiovascular disease, likely by flushing away its harmful cousin.

But finding such drugs has been a challenge. One promising, high-profile candidate from Pfizer, called torcetrapib, was pulled from development last year when clinical trials revealed serious safety concerns. And derivatives of niacin, a B vitamin shown to boost good cholesterol, has problematic side effects that stop many people from taking the drug.

New research from Leonard Guarente at MIT could provide a new target for HDL-raising drugs: the sirtuins, a class of genes linked to longevity. (See “The Enthusiast” and “The Fountain of Health.”) According to Guarente, SIRT1 can promote formation of good cholesterol and lowers the cholesterol burden in tissues by removing excess cholesterol from those tissues and flushing it out of the body. The findings were published today in the journal Molecular Cell.

Sirtris Pharmaceuticals, a company based in Cambridge, MA, that’s developing novel compounds that target the sirtuins, has already licensed the patent covering the research from MIT. Sirtris already has one sirtuin-activating compound in early clinical trials for diabetes.

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