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Regulus Therapeutics and Collaborators from NYU Langone Medical Center Publish New Data Demonstrating Clearance of Cholesterol from Bloodstream and Reduction of Atherosclerotic Plaques through Inhibition of microRNA-33
Date:6/6/2011

cine at Regulus. "These studies establish that antagonizing miR-33 with therapeutic anti-miR oligonucleotides can promote regression of atherosclerosis by increasing levels of HDL-C and promoting reverse cholesterol transport. This new paper, and others we have published recently, supports the development of anti-miR-33 as a potential new therapeutic for dyslipidemias, atherosclerosis, and other related metabolic diseases."

In the study, the impact of miR-33 inhibition was evaluated in low density lipoprotein cholesterol receptor deletion (LDLR-/-) hypercholesterolemic mice with already established atherosclerosis to more closely resemble patients in a clinical setting. The mice were treated weekly for four weeks with subcutaneous injections of 10 mg/kg of anti-miR-33 or control anti-miR oligonucleotides. Anti-miR-33 treatment increased HDL-C and enhanced cholesterol transport from peripheral cells to the liver for further excretion into bile and feces. In addition, anti-miR treated mice had a 35% reduction in lesion area of atherosclerotic plaques. Taken together, the results indicated that anti-miR-33 treatment supports the efflux of cholesterol from lesional macrophages and promotes regression of established atherosclerosis. Importantly, no elevations in serum hepatotoxicity markers, aspartate aminotransferase or alanine aminotransferase (AST/ALT) were observed.  

"Our studies with Regulus show that miR-33 inhibition raises circulating HDL-C, promotes removal of excess cholesterol from atherosclerotic plaques, and favorably affects lesion pathology," said Dr. Moore of NYU Langone. "The data establish miR-33 as an attractive therapeutic target for the treatment of atherosclerotic disease."

Regulus controls fundamental patent rights related to miR-33, including the miR-33 sequence and complementary sequences covered in the Tuschl III patent series. Additional Regulus patent rights include compositions of matter for various chemically modif
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SOURCE Regulus Therapeutics Inc.
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