Long-term gene therapy has found to be effective in improving cardiac function and reversing heart damage in heart failure.
During the study, the researchers treated the rats 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 and enhanced GRK enzymatic activity contributes to the deterioration of the heart in heart failure,
"The theory is that by inhibiting this kinase, the heart will recover partially due to reversal of the desensitization of the ?-adrenergic receptors," said Walter J. Koch, Ph.D., the W.W. Smith Professor of Medicine and the director of the Centre for Translational Medicine at Jefferson Medical College of Thomas Jefferson University.
"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," he added.
In the study, two groups of rats 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.
The researchers found that the rats who received the ARKct had a significantly increased left ventricular ejection fraction. The treatment also reversed the left ventricular deterioration and normalized the neurohormonal status.
Dr. Koch said that targeting the GRK2 enzyme with ARKct was sufficient to reverse heart failure even without concomitant metoprolol.
On the other hand, rats that received GFP or saline alone experienced more deterioration of cardiac function during the course of the study.
"Our data show that beta blockers and the ARKct peptide are compatible and can be given together," Koch said.
"Although beta blockers are effective at stopping the downward progression of the disease, they do not reverse the damage already done. That is where the ARKct gene therapy comes in," he added.
The study was published online in Circulation.