Delivery of a specific cholesterol-clearing gene into mice via gene therapy appears to reduce high cholesterol and virtually eliminate fatty plaques that are similar to those in the arteries of humans with heart disease, researchers report.

In the new study, Dr. Nicolas Duverger of Gencell in France, and Dr. Caroline Desurmont of Institut Pasteur in Paris, France and colleagues looked at mice genetically engineered to lack apolipoprotein E (apoE), an important cholesterol-clearing protein. The lack of apoE causes mice to have extremely high cholesterol levels and to develop fatty streaks and plaques in blood vessels in the first 4 months of life.

The researchers delivered the gene for apoE into the mice by attaching a functional copy of the apoE gene to a cold virus and injecting it into the mice. The mice also lacked a functioning immune system so that they did not destroy the cold virus, a common occurrence in gene therapy trials.

Mice injected with the apoE gene had a substantial drop in their cholesterol level. Although cholesterol levels began to rise within a few months, reinjection of the gene-carrying virus reduced the levels to normal again.

During the 28-week study, apoE-deficient mice had a 6-fold increase in fatty lesions in their arteries. In contrast, the fatty plaques in mice treated with gene therapy shrank to only 13% of their pretreatment size. Overall, the treated mice had lesions only 2% of the size of the plaques seen in untreated mice of the same age, according to the report in the February issue of Arteriosclerosis, Thrombosis, and Vascular Biology: Journal of the American Heart Association.

The authors conclude that gene therapy with apoE can both reduce cholesterol levels and reverse the effects of atherosclerosis -- at least in mice.

Scientists may someday devise an apoE gene therapy for humans that could protect against heart disease, according to Duverger. "There is a medical need for effective new therapies to treat people with high cholesterol levels," Duverger said in a statement issued by the American Heart Association.

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