UCLA researchers engineer experimental drug for preventing heart failure after heart attacks
Scientists at the have developed a first-of-its-kind experimental therapy that has the potential to enhance heart repair following a heart attack, preventing the onset of heart failure.
Cardiovascular disease continues to be the world’s leading cause of death, contributing to one-third of deaths annually. After a heart attack, the heart’s innate ability to regenerate is limited, causing the muscle to develop scars to maintain its structural integrity. This inflexible scar tissue, however, interferes with the heart’s ability to pump blood, leading to heart failure in many patients — do not survive beyond five years. The need for innovative therapies is urgent.
The new therapeutic approach aims to improve heart function after a heart attack by blocking a protein called ENPP1, which is responsible for increasing the inflammation and scar tissue formation that exacerbate heart damage. The findings, published in could represent a major advance in post-heart attack treatment.
The research was led by senior author a professor of medicine and molecular, cell and developmental biology at UCLA.
“Despite the prevalence of heart attacks, therapeutic options have stagnated over the last few decades,” said Deb, who is also a member of the UCLA Broad Stem Cell Research Center. “There are currently no medications specifically designed to make the heart heal or repair better after a heart attack.”
The experimental therapy uses a therapeutic monoclonal antibody engineered by Deb and his team. This targeted drug therapy is designed to mimic human antibodies and inhibit the activity of ENPP1, which Deb had increases in the aftermath of a heart attack.
The researchers found that a single dose of the antibody significantly enhanced heart repair in mice, preventing extensive tissue damage, reducing scar tissue formation and improving cardiac function. Four weeks after a simulated heart attack, only 5% of animals that received the antibody developed severe heart failure, compared with 52% of animals in the control group.
This therapeutic approach could become the first to directly enhance tissue repair in the heart following a heart attack; an advantage over current therapies that focus on preventing further damage but not actively promoting healing. This can be attributed to the way the antibody is designed to target cellular cross-talk, benefitting multiple cell types in the heart, including heart muscle cells, the endothelial cells that form blood vessels, and fibroblasts, which contribute to scar formation.
Initial findings from preclinical studies also show that the antibody therapy safely decreased scar tissue formation without increasing the risk of heart rupture — a common concern after a heart attack. However, Deb acknowledges that more work is needed to understand potential long-term effects of inhibiting ENPP1, including potential adverse effects on bone mass or bone calcification.
Deb’s team is now preparing to move this therapy into clinical trials. The team plans to submit an investigational new drug, or IND, application to the U.S. Food and Drug Administration this winter with the goal of beginning first-in-human studies in early 2025. These studies will be designed to administer a single dose of the drug in eligible individuals soon after a heart attack, helping the heart repair itself in the critical initial days after the cardiac event.
While the current focus is on heart repair after heart attacks, Deb’s team is also exploring the potential for this therapy to aid in the repair of other vital organs.
“The mechanisms of tissue repair are broadly conserved across organs, so we are examining how this therapeutic might help in other instances of tissue injury,” said Deb, who is also the director of the at the David Geffen School of Medicine. “Based on its effect on heart repair, this could represent a new class of tissue repair-enhancing drugs.”
This article is republished from the . Read the original .
Enjoy reading ASBMB Today?
Become a member to receive the print edition four times a year and the digital edition monthly.
Learn moreGet the latest from ASBMB Today
Enter your email address, and we鈥檒l send you a weekly email with recent articles, interviews and more.
Latest in Science
Science highlights or most popular articles
Building the blueprint to block HIV
Wesley Sundquist will present his work on the HIV capsid and revolutionary drug, Lenacapavir, at the ASBMB Annual Meeting, March 7鈥�10, in Maryland.
Gut microbes hijack cancer pathway in high-fat diets
Researchers at the Feinstein Institutes for Medical Research found that a high-fat diet increases ammonia-producing bacteria in the gut microbiome of mice, which in turn disrupts TGF-尾 signaling and promotes colorectal cancer.
Mapping fentanyl鈥檚 cellular footprint
Using a new imaging method, researchers at State University of New York at Buffalo traced fentanyl鈥檚 effects inside brain immune cells, revealing how the drug alters lipid droplets, pointing to new paths for addiction diagnostics.
Designing life鈥檚 building blocks with AI
Tanja Kortemme, a professor at the University of California, San Francisco, will discuss her research using computational biology to engineer proteins at the 2026 ASBMB Annual Meeting.
Cholesterol as a novel biomarker for Fragile X syndrome
Researchers in Quebec identified lower levels of a brain cholesterol metabolite, 24-hydroxycholesterol, in patients with fragile X syndrome, a finding that could provide a simple blood-based biomarker for understanding and managing the condition.
How lipid metabolism shapes sperm development
Researchers at Hokkaido University identify the enzyme behind a key lipid in sperm development. The findings reveal how seminolipids shape sperm formation and may inform future diagnostics and treatments for male infertility.