Cardiovascular disease remains the leading cause of death worldwide, accounting for one-third of all annual fatalities. Following a heart attack, the heart's natural regenerative ability is limited, resulting in the formation of scar tissue to preserve structural integrity. However, this rigid scar tissue hampers the heart's ability to pump blood effectively, leading to heart failure in many patients, half of whom do not survive beyond five years. There is an urgent need for innovative therapies. Scientists have now developed a first-of-its-kind experimental therapy that has the potential to improve heart repair after an attack, thereby preventing heart failure.

The new therapeutic approach, developed by researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA (Los Angeles, CA, USA), focuses on enhancing heart function post-heart attack by blocking a protein known as ENPP1. This protein contributes to increased inflammation and scar tissue formation, which worsen heart damage. Their findings, published in Cell Reports Medicine, could mark a significant advancement in post-heart attack treatments. The experimental therapy utilizes a therapeutic monoclonal antibody engineered by the research team. This targeted drug therapy aims to mimic human antibodies and block ENPP1 activity, which the researchers previously identified as elevated after a heart attack.

In their experiments, the researchers found that a single dose of the antibody significantly improved heart repair in mice, preventing substantial tissue damage, minimizing scar tissue formation, and enhancing cardiac function. Four weeks after a simulated heart attack, only 5% of the animals treated with the antibody developed severe heart failure, compared to 52% in the control group. This innovative approach could be the first to actively promote tissue repair in the heart following a heart attack, contrasting with existing therapies that primarily focus on preventing further damage. This effectiveness is linked to the antibody's design, which targets cellular communication, benefiting various cell types in the heart, including cardiac muscle cells, endothelial cells that form blood vessels, and fibroblasts that contribute to scar formation.

Preliminary findings from preclinical studies also indicate that the antibody therapy safely reduced scar tissue formation without heightening the risk of heart rupture—a common concern after a heart attack. Nonetheless, the researchers recognize the need for further investigation into the potential long-term effects of inhibiting ENPP1, including possible adverse impacts on bone mass or calcification. The research team is preparing to advance this therapy into clinical trials. They plan to submit an Investigational New Drug (IND) application to the U.S. Food and Drug Administration this winter, with the aim of initiating first-in-human studies in early 2025. These studies will involve administering a single dose of the drug to eligible patients shortly after a heart attack, facilitating the heart's self-repair during the critical initial days following the cardiac event. While the current emphasis is on heart repair post-heart attacks, the research team is also investigating the therapy's potential applications for repairing 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 senior author Dr. Arjun Deb, a professor of medicine and molecular, cell and developmental biology at UCLA who led the research. “Based on its effect on heart repair, this could represent a new class of tissue repair-enhancing drugs.” 

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