Gene therapy restores normal heart beat

BOSTON, Feb. 25 (UPI) -- Genetic manipulation of the molecular controls for calcium flow in heart cells can help failing hearts beat normally, suggesting that gene therapy might some day replace mechanical-assist devices or heart transplants as an effective treatment for congestive heart failure.

Harvard heart researcher Dr. Roger Hajjar said many heart experts believe that calcium plays a crucial role in heart failure in the elderly. Specifically, Hajjar and others hypothesized that abnormal calcium flow inside heart cells impairs the ability of those cells to contract and relax -- or beat -- normally.

In a study published in the Feb. 26 issue of Circulation, Journal of the American Heart Association, Hajjar and researchers from Massachusetts General Hospital in Boston reported that they restored normal function to damaged heart cells by genetic manipulation of a cardiac protein called phospholamban, which works like a pump to regulate the flow of calcium inside heart cells.

"In people with heart failure, calcium flow is abnormal: there is too much calcium when the heart is relaxed and too little calcium when the heart contracts," Hajjar explained in an interview with United Press International.

Hajjar and his colleagues collected heart cells from nine patients who had advanced heart failure and who were waiting for heart transplants. These cells were injected with a genetic derivative of phospholamban called antisense phospholamban. The antisense gene transfer is designed to specifically block formation of phospholamban genes, he said.

"By delivering this specific genetic information to the cells we improved calcium movement in the cells and the cells were able to relax and contract normally," said Hajjar. He said the results confirm earlier studies conducted in rats and pigs.

Dr. Rose Marie Robertson, professor of medicine at Vanderbilt University School of Medicine, Nashville, Tenn., told UPI that the study is "really elegant because it dissects, out of several of the possible mechanisms, that one you could use to improve the function of failing (heart) cells."

Robertson, immediate past president of the American Heart Association, said however that the work is really "experimental" and cautioned that use in patients is unlikely in the near future.

Hajjar agreed that this genetic approach is at least five years away from clinical use. "And the first human studies will probably combine this gene transfer with another therapeutic approach, possibly a mechanical assist device," he said.

Dr. Ann Bolger, associate professor of medicine at the University of California, San Francisco, said the research suggests "a new avenue for treating heart failure."

Calling congestive heart failure "the American epidemic" and noting that there are now 4.5 million Americans with congestive heart failure, Bolger said that every time research turns up more information about the mechanics of heart failure "we have new opportunities for treatment." But Bolger, who is a national spokesperson for the AHA, also cautioned that since the research is based on work with cells, "not even beating hearts," it is unlikely to become a practical treatment option in the near future.

The National Institutes of Health, the British Heart Foundation and the Doris Duke Charitable Foundation jointly funded the study.

(By Peggy Peck in Cleveland, Ohio)