Using Gene Therapy to Reduce Restenosis

Originally Published MDDI April 2002

R&D DIGEST

Although angioplasty is among the most common treatments for atherosclerosis in coronary arteries, one-third of all patients who receive balloon angioplasty experience restenosis within weeks or months of the procedure. Research has focused on developing methods to reduce or eliminate the potential for restenosis, including drug-eluting stents and radiation therapy.

Now bioengineers at the University of California, San Diego (UCSD) Jacobs School of Engineering have developed an experimental approach using gene therapy to prevent blockage of arteries following angioplasty. The patented therapy was shown to reduce restenosis by more than 50% in large-animal models.

According to Shu Chien, MD, professor of bioengineering and medicine, and director of the Whitaker Institute of Biomedical Engineering at UCSD, "In some sense, the procedure of angioplasty is tailor-made for delivering gene therapy." He explains that "the therapeutic genes can be given through the catheter during angioplasty, so no additional invasive procedures are required. During angioplasty, the arteries being treated are clamped to reduce blood flow. By isolating the arteries in this way, it allows localized delivery of the therapeutic agent and avoids potential complications caused by action elsewhere in the body."

The gene therapy technique uses RasN17, which is a negative mutant of the RAS protein that Chien found to contribute to restenosis. Chien's animal studies have shown that by introducing RasN17 during the angioplasty procedure, the gene therapy can prevent restenosis. The action of the therapeutic gene can be directly targeted to the smooth muscle cells, because these cells are exposed by the angioplasty procedure.

Chien selected pigs for the study because the porcine cardiovascular system is similar to that of humans. In his experiments, pigs received a balloon angioplasty procedure at the coronary artery. A subset of the pigs also received RasN17 via a catheter. The pigs that received RasN17 had 56% less artery wall thickening than those that received a placebo.

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