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How gene therapy could cure heart attack damage

Kathleen Blanchard's picture
Gene therapy could someday repair damaged hearts

Weill Cornell Medical College, Baylor College of Medicine and Stony Brook University Medical Center researchers have made a major advance in heart disease using gene therapy.The finding could mean a 'cure' for heart attack victims who suffer limitations.

The scientists have found a cocktail of 3 genes that can turn scar tissue from heart attack back into a healthy functioning muscle. Adding one extra gene improved heart function in rats even more than anticipated.

When heart attacks occur damage can be minor to extensive. When too much heart muscle is lost to scarring, congestive heart failure can ensue. Quality of life declines from lack of energy, shortness of breath and the need for multiple medications that can become an individual and economic burden.

Findings published in the Journal of the American Heart Association, show adding a gene that stimulates the growth of new blood vessels enhances the effect of gene therapy for repairing damaged heart muscle.

Dr. Todd K. Rosengart, chair of the Michael E. DeBakey Department of Surgery at BCM and the report's corresponding author said in a press release: "The theory is that if you have a big heart attack, your doctor can just inject these three genes into the scar tissue during surgery and change it back into heart muscle. However, in these animal studies, we found that even the effect is enhanced when combined with the VEGF gene."

When the scientists transferred several two genes into damaged rodent hearts, they discovered the result was improved cardiac function, measured by ejection fraction (EF) – the amount of blood the heart ejects with each contraction.

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Boosting EF is a goal of medical therapy for patients suffering from heart disease. When more blood is pumped into the circulation the organs receive more oxygen and nutrients that translates to better physical function.

The scientists injected either three forms of the VEGF gene that stimulates blood vessel growth or an inactive substance directly into damaged heart of rats for the study.

Three weeks later they received a 3-gene cocktail called GMT that included Gata4, Mef 2c and Tbx5.

Rats who received the GMT genes had a reduction in scar tissue of 50%. But adding VEGF quadrupled the effect, boosting heart function even further.

The researchers explain they used the GMT cocktail to avoid concerns over stem cell therapy that can lead to tumors.

The authors acknowledge more studies are needed to find out if the effect of VEGF combined with the gene cocktail is ‘real’. The gene therapy shows promise for patients who have suffered heart attack that can cause severe damage and lead to other complications as well from physical limitations.

Journal of the American Heart Association
January 4, 2013

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