Study: Gene Therapy significantly eases untreatable heart disease

Wednesday, November 20th 2002, 12:00 am

By: News On 6

CHICAGO (AP) _ The largest study yet of gene therapy for heart disease shows the approach can significantly relieve severe chest pain, though the improvements may take months to become apparent.

Researchers have been working for several years on the idea of injecting genes directly into the heart to improve blood flow. Several smaller studies have suggested a benefit, but the latest experiment is the first to subject the approach to a careful comparison with standard treatment.

``This is the first trial to provide a clear indication of efficacy of gene therapy,'' said Dr. Duncan Stewart, cardiology chief at St. Michael's Hospital in Toronto.

Several teams around the world are competing to prove the benefits of various combinations of genes for people with severe chest pain that cannot be treated with drugs, angioplasty of bypass surgery. All involve delivering genes to the heart to promote the growth of new blood vessels to carry nutrition and oxygen to starved heart muscle.

Stewart's study was financed by GenVac Inc. of Gaithersburg, Md. He presented the results Wednesday at the annual scientific meeting of the American Heart Association.

Unlike earlier studies reported so far, Stewart's experiment randomly assigned 71 volunteers to have either gene therapy or receive the usual medical treatment. After three months, there was no difference. However, by six months, people who got the gene therapy could walk significantly farther on a treadmill.

``It was surprising how much better the patients felt,'' Stewart said. One man was so sick he could not play with his grandchildren. After the treatment, ``he could enjoy his family and was just thrilled by that.''

To deliver the therapy, doctors opened the patients' chests and injected the growth hormone genes 30 times into the patients' hearts. The operation itself was fatal to two of the volunteers.

After they recovered, the patients walked on treadmills until their electrocardiograms showed clear signs of oxygen deprivation. The treadmill time improved by one minute in the gene therapy patients but was unchanged in the comparison group. The gene patients could also walk 25 percent longer before getting intolerable chest pain.

The doctors also took nuclear scans of the patients' hearts, intended to show changes in their blood flow. Some earlier experiments have shown this improves after gene therapy, and those data will be available soon in the Canadian experiment.

One drawback of the study is that patients knew, because of the operations, whether or not they received the genes, and this could have affected their sense of improvement. A new study will deliver the genes with a catheter threaded into the heart, and a sham procedure will be done on the comparison group, so no one will know who actually got the genes.

``It shows feasibility,'' Dr. Augustus Grant of Duke University, president-elect of the heart association, said of the latest study. ``The increase they saw in treadmill time is significant.''

Among other studies at the conference:

_ Doctors from the University of Leipzig in Germany compared the effects of balloon angioplasty against an exercise program in 101 people with stable heart disease. They found that after a year, 88 percent of people trained to ride an exercise bike 20 minutes a day were free of major complications, such as heart attacks and repeat hospitalization, compared with 70 percent of those who got angioplasty.

Dr. Stephan Gielen said a larger study will test whether the approach is safe. ``I would not advise patients to go home from an angiogram'' _ a common diagnostic procedure _ ``buy a bicycle and start training. We're not at that point yet,'' he said.

_ Dr. Russell V. Luepker of the University of Minnesota looked at the effect of exercise on medical costs on Medicare patients. Healthy people who did nothing ran up average bills of $11,300 during five years in the early 1990s, while those who got even modest exercise had bills of $6,800.

_ A study from the Hellenic Heart Foundation in Glyfada, Greece, shows that exercise significantly lowers C-reactive protein, a sign of inflammation that increases the risk of heart attacks. Men who worked out three times a week had levels 10 percent lower than sedentary people, and women's were 17 percent lower.