Gene Therapy May Heal Heart Damage

(HealthScout) -- In the not-so-distant future, gene therapy may be able to repair heart damage in people with congestive heart failure.

Currently, the only real hope for people with this ultimately fatal disease is a new heart.

But a new Duke University study says that, in tests on rabbits, a gene introduced directly into the damaged animals' hearts can reverse cell damage within the organ.

The researchers, whose previous studies on rabbits already have shown that gene therapy can prevent such damage, believe that one day gene therapy could be used to treat heart damage, and in people, not just animals.

In people with congestive heart failure, the heart muscle cannot stretch and contract normally, usually because of coronary artery disease or a heart attack. People are left feeling fatigued and weakened by even the simplest day-to-day activities.

Roughly 550,000 new cases of congestive heart failure are diagnosed every year in the United States, and nearly 47,000 people die each year from the condition. Between 1979 and 1998, the number of deaths from this disease increased by 135 percent.

The latest findings build on work done over the last eight years at Duke, including senior investigator Walter Koch's investigations of an enzyme called beta-adrenergic receptor kinase, or BARK. In a healthy heart, this enzyme helps restore normal muscular contractions after a release of adrenaline kicks the heart into high gear.

Adrenaline speeds up the heart by binding to beta-adrenergic receptors on heart cells. A few minutes of adrenaline-fueled high-energy output, which can make the heart pump up to five times faster than normal, is safe. But continued fast pounding leads to heart failure.

Koch, an associate professor of experimental surgery, had found that failing heart tissue contains levels of BARK three times higher than normal. If that compound could be controlled, he thought, perhaps it would be possible to reduce the over-production of BARK.

But because no chemical inhibitors exist to do that, Koch says, the researchers looked to a genetic solution to boost the heart's ability to pump blood.

Using a catheter, they inserted the gene for a BARK inhibitor, known as BARKct, into a harmless virus that could, in essence, "infect" the rabbits' heart cells and release the inhibitor. They then directed it into the coronary arteries of the left ventricles of rabbits that had experienced a heart attack. The virus, they say, did not cause inflammation or an immune response in either the animals that received the "infected" virus or in a smaller group that received an empty virus.

After one week, the researchers could see a "significant" improvement in left ventricular function in the rabbits that had received the BARKct gene, Koch says.

"After the introduction of the BARKct, they stopped getting worse and appeared to get better," he says. They still had damage from the heart attack, but "the hearts began to return to normal function," he says. Details appear in today's issue of the journal Circulation.

Dr. James Willerson, medical director of the Texas Heart Institute in Houston, calls the findings "provocative" and "encouraging."

Although he cautions that the results come from an experimental animal study and that more research will be needed to see if the procedure is safe and effective in people, Willerson adds that "inhibitors of BARK, such as the one used in this study, might be useful in the treatment of heart failure that is associated with increases in BARK."

Koch, who hopes to begin testing the technique in people within three years, believes it could have concrete clinical uses.

"There are certainly no cures for heart failure, besides a new heart," he says. Drugs known as ACE inhibitors and beta-blockers have been proven effective, and Koch says he's currently comparing the effects of BARKct vs. these drugs in mice.

"Our first target would be in patients who have severe heart failure who are awaiting transplantation," he says.

"A lot of people die while they wait for a heart since there aren't enough to go around," Koch says. "What's called a 'bridge to transplant' is needed.' "

And ultimately, he says, the procedure has the potential to reduce the need for transplants.

To learn more about congestive heart failure, visit the American Heart Association, the Heart Information Network or the Heart Failure Society of America online.

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