Gene Transfer for Heart Failure Shows Promise

Intracoronary gene transfer among heart failure patients increased left ventricular function beyond standard heart failure therapy.

Intracoronary gene transfer among heart failure patients increased left ventricular function beyond standard heart failure therapy though a single gene transfer administration, according to a new study published in JAMA Cardiology. Gene transfer involves introducing genes into cells so that the cells produce certain proteins—in this case, the protein adenylyl cyclase type 6 (AC6), which preliminary studies suggest may benefit heart muscle cells. The amount and function of AC6 are reduced in heart failure. The gene is introduced into the heart cells by an adenovirus that has been modified (adenovirus 5). Adenoviruses are the most commonly used vector in clinical gene transfer.

H. Kirk Hammond, MD, of the Veterans Affairs San Diego Healthcare System, and colleagues randomly assigned 56 patients (males and nonpregnant females ages 18 to 80 years of age) with symptomatic heart failure and an ejection fraction (EF; a measure of how well the left ventricle of the heart pumps with each contraction) of 40% or less to receive 1 of 5 doses of adenovirus 5, which coded for AC6, or placebo. Patients were from 7 US medical centers and were followed for up to 1 year. Patients were required to have an implanted cardiac defibrillator and at least one major coronary artery or graft with less than 50% obstruction.

The study’s main objective was to assess the safety of one-time injection of adenovirus 5 in heart failure patients and to identify effective doses for future trials. The investigators found that the AC6 gene transfer created a beneficial effect on cardiac function that was related to the dose administered and was deemed safe in patients with heart failure and reduced EF. Heart failure admission rate was 9.5% in participants who received AC6 and 28.6% in those who received placebo (P = .10). The rates of serious adverse events were similar in both groups.

Although the 1-year mortality rate was lower in participants who received AC6 gene transfer, the number of events was too low to draw a conclusion. The researchers found that participants with nonischemic heart failure (heart failure not due to coronary artery disease) who received AC6 had increased EF, and they suggest targeting the gene therapy to this group of patients, who will likely have the most benefit.

The investigators concluded that AC6 gene transfer safely increased left ventricular function beyond optimal heart failure therapy through a single administration, and they recommend that larger trials of the gene transfer are warranted to assess the safety and efficacy of AC6 gene transfer for patients with heart failure.

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