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Gene Therapy Helps Ailing Heart

Rat study shows function, survival improve after treatment

MONDAY, Sept. 17, 2001 (HealthDayNews) -- Gene therapy to help heart muscle produce more calcium can greatly improve the organ's function and prolong survival in rats with heart failure, a new study says.

The scientists, led by Harvard University researchers, have already shown that their approach can restore heart power in human cells, though it hasn't yet been tested in patients. But since a number of drugs that boosted heart output also proved to shorten life expectancy, a worry had been that the gene therapy might be vulnerable to the same unfortunate trade-off. The latest findings, which appear in the Sept. 18 issue of Circulation: Journal of the American Heart Association, suggest that it is not.

Heart failure is a leading cause of death in this country, diagnosed in 550,000 people each year and affecting 5 million Americans overall, according to the American Heart Association. The disease is the result of flaccid muscles that help the heart pump. When they weaken further, blood backs up in the vessels that bring it from the lungs, which in turn fill with fluid that cripples breathing.

Heart failure has no cure, and deaths from the disease have doubled since 1975 despite advances in treatment that reduce -- but don't reverse -- progression of the condition.

To achieve good muscle action, the heart needs calcium ions, which in turn are regulated by a protein "pump" called SERCA2a, controlled by a gene of the same name. In patients with heart failure, the protein pump underachieves. So spurring heart muscle to produce more SERCA2a can in principle -- and in practice, too -- restore the calcium cycle to its normal state and allow the organ to function properly again.

A research team led by Dr. Roger Hajjar, a gene therapy expert at Massachusetts General Hospital, has applied this approach. He and his team used a neutralized virus to shuttle an extra copy of SERCA2a into the heart muscle of rats with a condition that mimics human heart failure. They also gave dummy injections to rodents with the same disease.

The gene therapy significantly boosted heart output, compared with untreated animals, Hajjar says. But equally important, he says, it prolonged their lives. A month after the treatment, 63 percent of the animals that received the new SERCA2a genes were alive, compared with just 9 percent of untreated rats -- a seven-fold difference.

"We got an improvement in the strength of the heart, but we also got a tremendous survival benefit," Hajjar says.

Rejuvenating the heart carries the added benefit of easing the stress on other organs affected by heart failure, such as the lungs, liver and kidneys, Hajjar says.

The researchers are now in the process of designing a study to test their approach in pigs. If that's a success, they hope to start applying it to people with heart failure "in a few years," Hajjar says. The cardiovascular system in pigs has similarities to that of humans, making the animal a prime choice in these types of experiments.

However, gene therapy has had several highly public failures in the last year or so, including the death of an 18-year-old Pennsylvania man that prompted a temporary halt on human trials with the technology.

In the meantime, researchers, including cardiologists, have been intensely focused on the virtues of stem cells to repair diseased, damaged or otherwise failing organs, including the heart. Indeed, many scientists believe that stem cells will ultimately make gene therapy a medical museum piece that became archaic before it even saw widespread action in patients. Stem cells are primitive "master" cells that can turn into any kind of tissue.

But Dr. Michael Bristow, head of cardiology at the University of Colorado in Denver, says reports of gene failure's obsolescence are premature. "I don't think there's been any loss of enthusiasm for gene therapy," says Bristow, who admits that the Pennsylvania death was a "major blow" to the field. As for the latest work, Bristow says, "there's a sense that this certainly has an upside."

Bristow, a co-founder of the Heart Failure Society of America, says the most likely application of the approach would be in patients with advanced-stage heart failure who are waiting for a transplant, offering a potentially cost-effective alternative to current devices that assist the pump.

Before then, he says, researchers will need to demonstrate several things, including how much function can be restored and what is the ideal "vector," or viral delivery system, for the therapeutic gene.

What To Do

To find out more about heart failure, try the American Heart Association or Heart Failure Online.

The Heart Failure Society of America is also a good source for information about the disease.

SOURCES: Interviews with Roger Hajjar, M.D., assistant professor, Harvard University School of Medicine, Massachusetts General Hospital, Boston; and Michael Bristow, M.D., head of cardiology, University of Colorado Health Science Center, Denver; Sept. 18, 2001 Circulation: Journal of the American Heart Association
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