Gene Therapy Safe and Effective for Chest Pain
Feb. 25, 2002 -- Gene therapy, in which the genes for growth factors are transferred into the oxygen-starved hearts of people with angina, eases their debilitating chest pain and allows them to exercise longer, according to results of the first clinical trial of gene therapy.
When blood vessels to the heart become blocked, not enough oxygen-rich blood gets to the heart tissue. This causes chest pain, known as angina, especially during physical exertion. At first, the body compensates for the reduced blood flow by creating many tiny vessels to help take up the slack. But for some reason, this response, called angiogenesis -- the formation of new blood vessels -- doesn't last. Triggering angiogenesis with medicine has been tricky.
"There is no product approved to stimulate the growth of new blood vessels," says study author Cindy Grines, MD, director of the cardiac catheterization laboratories and the interventional cardiology training program at William Beaumont Hospital in Royal Oak, Mich. "We think the growth factor gene used here restarts this natural process. This is a completely new and different approach."
Scientists have long been searching for ways to induce angiogenesis, but until now, they haven't had much luck. When they injected angina patients' hearts with growth proteins (that cause the growth of blood vessels and the product of growth factor genes), the results didn't last. The body quickly used up the proteins and the effect was lost.
In this most recent study, Grines' team injected 60 heart disease patients with the gene that makes growth protein, rather than the protein itself. Nineteen volunteers received a placebo injection. The men and women averaged 60 years old. About half had already had a heart attack, and a quarter had had bypass surgery to treat heart disease. Most had suffered from angina for several years.
Each patient underwent treadmill testing to see how long he or she could walk. Four weeks into the study, patients who'd received the growth gene were able to walk 1.3 minutes longer than they originally had, compared with an improvement of only 0.7 minutes for patients who'd received the placebo. What's more, the sickest patients showed the most dramatic improvements.
According to Grines, the patients' heart muscles were able to incorporate the gene, churning out blood-vessel generating proteins for several weeks.
"The results of this study are very encouraging because the response that we saw was far in excess of what we would have expected," says study co-author Robert L. Engler, MD, a cardiologist at the Veterans Administration San Diego Health Care System. Our estimate was that we would have needed a lot more patients to detect any effect," he says in a news release.
Still, the researchers say, to show effectiveness, these results need to be replicated in a much larger group of patients. That large-scale trial is already under way at 100 U.S. centers.