A novel therapeutic approach developed by UCLA researchers shows promise in preventing heart failure following a heart attack. The experimental therapy, a monoclonal antibody, targets the ENPP1 protein to enhance heart repair and reduce scar tissue formation. This innovative treatment could represent a significant advancement in post-heart attack care, addressing the critical need for therapies that actively promote healing.
Targeting ENPP1 to Enhance Heart Repair
Cardiovascular disease remains the leading cause of death worldwide. After a heart attack, the heart's ability to regenerate is limited, often leading to scar tissue formation that impairs cardiac function and can result in heart failure. Current therapies primarily focus on preventing further damage, but do not actively promote tissue repair. The new therapy aims to change this paradigm by blocking ENPP1, a protein that exacerbates inflammation and scar tissue formation.
According to Arjun Deb, 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. There are currently no medications specifically designed to make the heart heal or repair better after a heart attack."
The experimental therapy utilizes a therapeutic monoclonal antibody engineered to inhibit the activity of ENPP1. Deb's previous research established that ENPP1 levels increase after a heart attack, contributing to tissue damage.
Preclinical Evidence of Improved Cardiac Function
In preclinical studies, a single dose of the antibody significantly enhanced heart repair in mice following a simulated heart attack. The treatment prevented extensive tissue damage, reduced scar tissue formation, and improved cardiac function. Notably, only 5% of animals treated with the antibody developed severe heart failure, compared to 52% in the control group four weeks after the event.
This therapeutic approach enhances tissue repair by targeting cellular cross-talk, benefiting multiple cell types in the heart, including heart muscle cells, endothelial cells, and fibroblasts. Initial findings also indicate that the antibody therapy safely decreased scar tissue formation without increasing the risk of heart rupture, a common concern post-heart attack.
Path to Clinical Trials
Deb's team is preparing to submit an Investigational New Drug (IND) application to the FDA this winter, with the goal of initiating first-in-human studies in early 2025. These trials will assess the safety and efficacy of a single dose of the antibody administered shortly after a heart attack to promote heart repair during the critical initial days. While the initial focus is on heart repair, the team is also exploring the potential of 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. "Based on its effect on heart repair, this could represent a new class of tissue repair-enhancing drugs."
