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Heart Failure Gene
January 10, 2000
Failing myocyte beingTreated
image: Dr. Roger Hajjar

Congestive heart failure (CHF) is a growing epidemic in the United States. Nearly five million people in the US suffer from this condition, and the percentage of CHF deaths has more than doubled in the past twenty years. But while current therapies can slow the progression of the disease, a cure has remained elusive.

Now, scientists at Harvard Medical School have developed a way to insert genes into failing heart cells that can reverse the damage of congestive heart failure.

How’d They Do It?

The research team found that CHF patients have a number of abnormalities within their individual heart cells. One of these abnormalities is a deficiency of a protein, called SERCA2a, that acts as a pump to restore normal calcium levels in the heart cells after each contraction. When the cells stop producing enough of this protein, the calcium accumulates, causing the heart to contract slowly and weakly. This causes symptoms such as shortness of breath, chest pain, and swelling in the legs.

Dr. Roger Hajjar, a researcher involved in the hea

"We restored this pump back to normal by putting the gene that manufacturers that pump into the cell," explains Dr. Roger Hajjar, one of the researchers involved in the study. "By doing so, the cell that came from a failing heart contracted to normal levels."

So far, the experiments have been limited to animals (with living animal models of heart failure) and individual heart cells contributed by human donors. The treatment restored the strength of contraction to normal levels within 24 hours. In the small population of animals tested so far, the treatment doubled the chance of survival as compared with the untreated animals. The scientists reported their preliminary results in the December 7, 1999, issue of the journal Circulation.

Is There A Downside?

One of the main limitations of this technique is the method of delivering the gene to the proper target. The genes were delivered with the first generation adeno-viruses, or cold viruses, which are not very specific and can infect every cell in the body. To account for this, researchers are looking for tissue specific genes that may be inserted into every cell, but only get turned on in the heart cells.

In addition, even though the adeno-viruses are harmless to the cell, they are easily detected by the bodyÍs immune system, which is able to get rid of the virus within a few weeks to a month. Dr. Hajjar is hoping to find a new delivery system that cannot be detected by the immune system.

"Obviously, we would need to test this in patients and see the long term consequences of this type of treatment," says Hajjar. "But clearly it offers us a hope that this will be a new target that will have beneficial effects in the treatment of heart failure."

Elsewhere on the Web

The American Heart Association

Map of the Human Heart






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