(PHILADELPHIA) Long-term gene therapy resulted in improved cardiac function and reversed deterioration of the heart in rats with heart failure, according to a recent study conducted by researchers at Thomas Jefferson University's Center for Translational Medicine. The study was published online in Circulation.
The rats were treated with a gene that generates a peptide called ARKct, which was administered to hearts in combination with recombinant-adeno-associated virus serotype 6 (rAAV6). ARKct works by inhibiting the activation of G protein-coupled receptor kinase 2 (GRK2).
GRK2 is a kinase that is increased in heart failure myocardium. Enhanced GRK enzymatic activity contributes to the deterioration of the heart in heart failure, according to Walter J. Koch, Ph.D., the W.W. Smith Professor of Medicine and the director of the Center for Translational Medicine at Jefferson Medical College of Thomas Jefferson University. Dr. Koch's research team carried out the study, which was led by Giuseppe Rengo, M.D., a post-doctoral fellow.
"The theory is that by inhibiting this kinase, the heart will recover partially due to reversal of the desensitization of the -adrenergic receptors," Dr. Koch said. "The expression of ARKct leads to a negative neurohormonal feedback that prevents the heart from continuing on the downward slope during heart failure. This was one novel finding of the study."
Dr. Koch and his colleagues used five groups of rats in their study. Two groups received rAAV6 with the ARKct peptide, two groups received rAAV6 with green fluorescent protein (GFP), and the last group received a saline treatment. One of the ARKct groups and one of the GFP groups also received the beta blocker metoprolol concurrently.
Twelve weeks after receiving the treatment, the rats who received the ARKct had a significantly increased left ventricular ejection fraction. The
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Thomas Jefferson University