Innovative Gene Therapy Enhances Heart Function in Primates Post-Heart Attack

Researchers at Duke University have made significant advances in gene therapy aimed at repairing heart damage caused by heart attacks in nonhuman primates. This groundbreaking study marks the first instance of utilizing gene therapy to restore heart functionality in such animal models, providing hope for future human applications.

Each year, over 800,000 individuals in the United States experience heart attacks. While many survive the initial event, the resulting damage to the heart muscle is typically irreversible, since cardiac cells lack the ability to regenerate naturally. This damage can lead to weakened heart contractions, increasing the risk of heart failure and potentially fatal arrhythmias. Existing treatments primarily focus on slowing the progression of heart disease rather than restoring lost heart function.

In this study, researchers successfully employed an engineered bacterial sodium channel to restore electrical and mechanical function in damaged heart tissues. Initially, the team demonstrated that this approach improved the contraction strength of lab-grown human heart tissues. In subsequent trials involving macaque monkeys with heart conditions resembling those seen in human heart attacks, the gene therapy effectively restored the heart's pumping ability and mitigated arrhythmias within weeks of treatment.

According to the lead researchers, this dual-action strategy has shown promising results. The therapy not only enhances the heart's electrical function but also improves its mechanical performance, potentially offering advantages over other current therapeutic methods. The exciting outcomes have paved the way for plans to progress to human clinical trials.

Prior investigations by the Duke team established a proof-of-concept demonstrating that bacterial genes could be delivered to the heart using viruses commonly utilized in clinical settings. This method was chosen due to the smaller size of bacterial genes, which can be accommodated by the delivery system, unlike larger human sodium channel genes.

The recent research, conducted in collaboration with experts from Singapore, involved the direct injection of this gene therapy into the damaged areas of the monkeys' hearts. Notably, the delivered genes were localized to the intended sites, with no adverse side effects reported during the study.

One of the researchers highlighted that the treatment significantly improved heart function under pathological conditions, utilizing a dosage that was 100 times lower than what is currently approved for clinical use. Additionally, this method can be administered via catheter, eliminating the need for invasive open-heart surgery.

The team acknowledges that various clinical trials are in progress to explore gene therapy for specific genetic heart diseases, improve calcium signaling, and induce heart muscle regeneration. However, this study stands out as the first to investigate gene therapy for heart disease within a nonhuman primate model. The researchers believe this innovative approach could be particularly effective in treating heart attacks and related fibrosis, as it also reduces the risk of arrhythmias.

Looking ahead, the research team is already conducting studies in pigs, which is a crucial step toward seeking FDA approval for initiating human trials.