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Lexicon Develops Antibodies That Lower Triglycerides and,Cholesterol as Potential New Therapy for Heart Disease

- Publication of New Cardiovascular Target from Lexicon's Genetic Research -

THE WOODLANDS, Texas, July 02, 2007 /PRNewswire-FirstCall/ -- Lexicon Pharmaceuticals, Inc. today reported results from preclinical research demonstrating that antibodies directed to a potential new target, angiopoietin-like protein 4 (ANGPTL4), rapidly lower triglycerides and cholesterol. Research suggests that a monoclonal antibody (mAb) targeting ANGPTL4 may have therapeutic application in the treatment of cardiovascular disease. The results appeared in an article, entitled "Lipid-lowering effects of anti-angiopoietin-like 4 antibody recapitulate the lipid phenotype found in angiopoietin-like 4 knockout mice," published in the July 10, 2007 edition of the journal Proceedings of the National Academy of Sciences.

Lexicon scientists first identified ANGPTL4 as a potential target for cardiovascular disease using the company's proprietary gene knockout technology. Lexicon scientists create animal models that have alterations in specific genes in order to discover the physiological and behavioral effects that result from the loss of the protein encoded by the gene. Researchers found that animal models in which the ANGPTL4 gene was knocked out had lower triglyceride and cholesterol levels than normal animals. The ANGPTL4 gene encodes a protein that is secreted into the bloodstream and is now believed to play an important role in triglyceride and cholesterol metabolism. Lexicon's biotherapeutics group developed a monoclonal antibody as an injectable agent targeting the ANGPTL4 protein to reproduce the triglyceride and cholesterol- lowering effects identified in the animal models. Notably, this appears to be the first successful production of a monoclonal antibody to this target.

"High triglycerides and cholesterol are correlated with an increased risk of heart disease," commented Dr. Brian P. Zambrowicz, executive vice preside
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