Jefferson scientists use gene therapy to reverse heart failure in animals

(PHILADELPHIA) Heart researchers at the Center for Translational Medicine at Jefferson Medical College have used gene therapy to reverse heart failure in animals. In addition, they found that this gene therapy strategy had "unique and additive effects" to currently used, standard heart failure drugs called beta-blockers.

Reporting in the American Heart Association journal Circulation, researchers led by Walter J. Koch, Ph.D., director of the Center for Translational Medicine and the George Zallie and Family Laboratory for Cardiovascular Gene Therapy in the Department of Medicine at Jefferson Medical College of Thomas Jefferson University in Philadelphia, used a virus to carry the gene for a protein, S100A1, into the heart cells of rats with heart failure. The virus expressed the S100A1 gene only in heart cells and not in other organs, essentially making it a tailored therapy. After 18 weeks, those animals that received the gene therapy had significantly improved heart function compared to animals that did not receive the treatment.

Specifically, the Koch team, including Patrick Most, M.D., and Joseph Rabinowitz, Ph.D., also in Jefferson's Center for Translational Medicine, experimentally produced heart failure in the animals, which is characterized by a dramatic reduction in the heart's pumping ability. The scientists then delivered a modified adeno-associated virus (AAV) that contained the S100A1 gene to the heart's coronary arteries with the help of a novel heart-specific "gene promoter" that enabled the gene to be present only in heart cells.

The rats with heart failure were then followed for another two months, when their heart pumping function was monitored again. The animals that received the gene therapy had significantly better heart-pumping abilities compared to the pre-gene therapy level, and overall, the S100A1-treated rats had improved heart health. The researchers found this in both individual heart cells and in the whole

Contact: Steve Benowitz
Thomas Jefferson University

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