Statin drugs, such as pravastatin and lovastatin, are a highly successful class of cholesterol-lowering medicines that prevent heart attack by reducing the amount of unhealthy fat circulating in the blood. They achieve this by blocking the liver enzyme, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. However, new research points to an anti-inflammatory effect of these drugs, and an article published in this month’s Nature Medicine (Vol. 7, No. 6, 01 Jun 2001) not only outlines how they suppress the inflammatory response, but also suggests that a new series of statin-like drugs could be developed with potential against autoimmune diseases such as psoriasis and theumatoid arthritis.
Gabriele Weitz-Schmidt and colleagues from Novartis Pharma AG in Switzerland, tested the ability of a range of statin drugs to bind to the integrin molecule leukocyte function antigen-1 (LFA-1) which is present on the surface of immune cells called leukocytes. LFA-1 interacts with intercellular adhesion molecule-1 (ICAM-1) to recruit leukocytes to sites of inflammation. By preventing the binding between LFA-1 and ICAM-1, statins block the inflammatory response.
The scientists went on to develop a molecule with enhanced binding affinity for the LFA-1 site but with reduced activity against HMG-CoA reductase. This compound, LFA703, almost completely blocked peritonitis in a mouse model, an effect which suggests that similarly-designed drugs may be effective in other inflammatory conditions.
Dr. Gabriele Weitz-Schmidt
Novartis Pharma AG
Tel: +41 61-324-9252
Fax: +41 61-324-9584
(C) Nature Medicine press release.
Message posted by: Trevor M. D'Souza
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