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Isis Reports Reduction of apoB-100 Levels in a Murine Model Resulting in Up to 92% Reduction of Atherosclerosis
Date:4/18/2008

CARLSBAD, Calif., April 18 /PRNewswire-FirstCall/ -- Isis Pharmaceuticals, Inc. (Nasdaq: ISIS) presented the results of two studies designed to assess the impact of lowering apoB-100 on atherosclerosis at the 2008 Annual Atherosclerosis, Thrombosis and Vascular Biology (ATVB) Conference in Atlanta, Georgia. The data were presented in a poster entitled "Antisense Inhibition of Apolipoprotein B Ameliorated Diet-Induced Hypercholesterolemia and Reduced Atherosclerosis in LDL Receptor-Deficient Mice" by Adam E. Mullick, Ph.D. of Isis yesterday at ATVB.

Both studies were performed in a murine model in which the LDL receptor, which is responsible for the maintenance of normal serum cholesterol levels, has been genetically eliminated. These animals have very high cholesterol levels (1,000 - 2,000 mg/dL on a high fat diet) and develop severe atherosclerosis. In the first study, the impact of treatment with an antisense drug was evaluated in the context of two atherogenic high fat diets. Animals on these diets had elevated total cholesterol and LDL-cholesterol levels that increased during the two weeks of high fat diet prior to drug treatment. These cholesterol levels dramatically decreased during the 10 week treatment period. At a dose of 50 mg/kg twice weekly, the murine apoB-100 antisense drug reduced total cholesterol and LDL-cholesterol by 87% and 93%, respectively. These reductions in cholesterol directly correlated with reduction in liver and plasma apoB-100 levels. Aortic atherosclerotic lesions were reduced by 78% - 92% in the same animals.

The second study, which evaluated the effects of increasing doses of drug on lipid levels, confirms and extends the results of the previous study, and showed that the effects of the apoB-
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SOURCE Isis Pharmaceuticals, Inc.
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