Gene therapy restores functionality in non-human primates after heart attacks

Biomedical engineers at Duke University have successfully conducted experiments to treat damage caused by heart attacks in non-human primates using gene therapy for the first time.

More than 800,000 Americans suffer a heart attack every year. Even if they survive the initial event, the damage to the heart is often permanent because heart muscle cells do not naturally regenerate. Patients are left with weakened heart contractions that can lead to heart failure or dangerous irregular heart rhythms called arrhythmia that can be fatal. Current therapies can only slow down disease progression and are limited in restoring lost function.

Now, researchers have shown they can help the heart to normalize strength and rhythm by delivering an engineered bacterial sodium channel to the damaged heart. The researchers first showed they can successfully improve contraction strength of injured lab-grown human heart tissues using these channels.  In subsequent studies in macaque monkeys with heart damage mimicking that found in human heart attack, the gene therapy largely restored the heart’s ability to pump blood and prevented arrhythmias within weeks of administration.

The results appeared online August 29 in the journal Circulation Research.

“This approach improved both the electrical and mechanical function of damaged heart tissue, which may have added benefits compared to other approaches being pursued,” said Nenad Bursac, professor of biomedical engineering at Duke. “We’re excited by the promising results of this two-pronged strategy and are on a path toward eventual human trials.”

In previous work, the Bursac group demonstrated proof-of-concept by showing that bacterial genes can be delivered to the heart by viruses commonly used in clinical settings. Bacterial genes were used because they are smaller than human sodium channel genes, which can not fit into these viruses.

The latest study, in collaboration with Lei Ye and researchers from Singapore, demonstrated that this form of gene therapy can be directly injected into the site of heart damage in monkeys to exert therapeutic effects. Importantly, the genes delivered were not found anywhere outside of their intended sites, and no adverse effects were observed during the study period.

“The treatment improved heart function in pathological conditions in a clinically relevant setting,” said Tianyu Wu, a postdoctoral researcher working in Bursac’s lab. “The dosage we administered is 100 times lower than what is clinically approved, and the delivery can be achieved through a catheter, avoiding the need to do open-heart surgery in patients.”

The researchers note that there are several similar ongoing efforts in clinics. Some clinical trials are investigating the use of gene therapy for specific heart genetic diseases. Others are focused on correcting calcium signaling to improve contractile strength of a failing heart. Yet another is trying to induce heart muscle to regenerate.

But to their knowledge, this is the first study that has tested gene therapy on a heart disease model in non-human primates. The team also believes that this approach may be particularly effective for heart attack and fibrosis because it also decreases incidence of arrythmias.

Moving forward, the team already has studies underway in pigs, which is a critical step toward getting FDA approval to begin human trials.

This research was supported by the American Heart Association, the National Institutes of Health (EB032726, HL126524, HL132389, HL134764), and Duke/Duke-NUS Research Collaboration Pilot Project.

“BacNav gene therapy improves function of infarcted engineered human myocardium and NHPs.” Tianyu Wu, Nicole G.Z. Tee, Yiu Yan Siu, Anna Tornatore, Abhishek Bhattacharjee, James Koconis, Szejie Loo, Liping Su, Binjie Li, Lei Ye, and Nenad Bursac. Circulation Research, 2025. DOI: 10.1161/CIRCRESAHA.125.326570