An innovative therapeutic monoclonal antibody treatment may soon be the first to boost tissue healing in the heart after a heart attack.
Researchers at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at UCLA have created a unique experimental therapy that could promote heart recovery following a heart attack, potentially preventing heart failure.
Cardiovascular disease remains the leading global cause of death, responsible for about one in three fatalities each year. Following a heart attack, the heart’s natural regenerative abilities are limited, leading to scar tissue formation to preserve its structure. Unfortunately, this rigid scar tissue hinders the heart’s capacity to pump blood effectively, resulting in heart failure in many individuals—half of whom do not survive beyond five years. Thus, there is an urgent need for new treatment options.
The new treatment strategy aims to enhance heart function after a heart attack by inhibiting a protein known as ENPP1. This protein leads to increased inflammation and scar tissue, which worsen heart injury. The results of this research, published in Cell Reports Medicine, could indicate a significant step forward in treating patients post-heart attack.
The research was spearheaded by Dr. Arjun Deb, a professor of medicine and molecular, cell, and developmental biology at UCLA.
“Although heart attacks are common, treatments have not advanced much in the last few decades,” Deb stated, also part of the UCLA Broad Stem Cell Research Center. “Currently, there are no medications specifically aimed at improving the heart’s healing or recovery after a heart attack.”
The experimental therapy involves a monoclonal antibody developed by Deb and his research team. This specialized drug is designed to act like human antibodies and block the activity of ENPP1, which Deb had found to be elevated after a heart attack.
The team discovered that a single dose of the antibody significantly improved heart repair in mice, leading to lesser tissue damage, reduced scar formation, and enhanced cardiac function. Four weeks post a simulated heart attack, only 5% of the mice treated with the antibody experienced severe heart failure, in contrast to 52% of those in the control group.
This therapy could potentially be the first to actively promote heart tissue repair after a heart attack, a significant improvement over existing treatments that primarily focus on preventing additional harm rather than facilitating healing. This success is linked to the antibody’s capacity to target cellular interactions, positively affecting various cell types in the heart, including cardiac muscle cells, endothelial cells that line the blood vessels, and fibroblasts, which are involved in scar formation.
Early results from initial studies also indicate that the antibody treatment reduces scar tissue formation without increasing the likelihood of heart rupture—a common risk following heart attacks. Nonetheless, Deb notes that further research is necessary to fully understand the potential long-term impacts of inhibiting ENPP1, particularly regarding the potential negative effects on bone density or calcification.
Deb’s team is preparing to advance this therapy to clinical trials. They plan to submit an Investigational New Drug (IND) application to the U.S. Food and Drug Administration this winter, aiming to initiate first-in-human trials in early 2025. These studies are intended to explore the effects of administering a single dose of the drug to eligible individuals shortly after experiencing a heart attack, assisting the heart’s self-repair during the critical days following the event.
While the primary focus is on heart recovery following heart attacks, Deb’s team is also investigating the potential of this therapy for repairing other essential organs.
“Tissue repair mechanisms are largely similar across various organs, so we are looking into how this therapy could aid in other situations of tissue damage,” said Deb, who also directs the UCLA Cardiovascular Research Theme at the David Geffen School of Medicine. “Given its effects on heart recovery, this might signify a new category of drugs designed to enhance tissue repair.”
The therapeutic candidate discussed in this research is patented by the Regents of the University of California. The treatment method has only been tested in preclinical settings and has not yet been evaluated for safety and efficacy in humans by the FDA.
Other contributors from UCLA include Shen Li, Bo Tao, Jijun Wan, Enca Montecino-Rodriguez, Ping Wang, Baiming Sun, Yiqian Gu, Sivakumar Ramadoss, Lianjiu Su, Qihao Sun, Johanna Ten Hoeve, Linsey Stiles, Jeffrey Collins, R. Michael van Dam, Mikayla Tamboline, Richard Taschereau, Orian Shirihai, Matteo Pellegrini, Thomas Graeber, Kenneth Dorshkind, and Shili Xu. Researchers Feiyang Ma from Northwestern University and Douglas B. Kitchen from Curia Global, Inc. also contributed to the study.
The study received funding from the National Institutes of Health, the California Institute for Regenerative Medicine, and the Department of Defense.
