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NOVEL HIGH-THROUGHPUT SCREENING ASSAY FOR IDENTIFICATION OF CHOLESTEROL INHIBITORS

Dartmouth scholars developed a high-throughput screen comprised of a cell-based assay for identification of chemical inhibitors which block internalization of plasma membrane cholesterol from entering the cell interior. Two novel cell lines originally developed at Dartmouth are used in this screen.

Agents identified as cholesterol inhibitors in accordance with this method can block the internalization of plasma membrane cholesterol from entering the cell interior thereby causing cholesterol to accumulate in the plasma membrane and promoting cholesterol efflux and stimulating reverse cholesterol transport in various body cells. These agents are expected to slow the development of atherosclerosis. Agents identified as inhibitors can also block the internalization of plasma membrane cholesterol in intestinal enterocytes, thereby preventing dietary cholesterol absorption. Such agents can also slow down the accumulation of amyloid beta-peptides in the brain, thereby slowing down the symptoms of Alzheimer’s disease. Accordingly, test agents identified as cholesterol inhibitors with this assay are expected to be useful in preventing and treating cardiovascular and neurodegenerative diseases associated with over accumulation of cholesterol in cells. Such agents are expected to be useful in the treatment of Niemann Pick type C disease, an autosomal recessive, neurovisceral disorder that affects children.

These findings are claimed in the issued United States Patent No. 7,049,086. We are seeking an industrial partner who is interested in their further refinement and commercialization. (Ref: J161)


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