Isis reports positive data from atherosclerosis study

Both studies were performed in a murine model in which the low-density lipoprotein (LDL) receptor, which is responsible for the maintenance of normal serum cholesterol levels, has been genetically eliminated. 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 50mg/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-100 antisense drug were linearly dose-dependent with regard to reductions on apoB-100 and atherogenic lipid levels, triglycerides, and atherosclerotic plaques. The maximum reduction of atherosclerotic plaques was 89% in this study.