West LA Times

Researchers at UCLA have developed an experimental therapy that could improve heart repair following a heart attack, potentially preventing heart failure. This new approach, led by Dr. Arjun Deb and his team at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, involves a monoclonal antibody therapy targeting the protein ENPP1.

ENPP1 is known to increase inflammation and scar tissue formation after a heart attack, worsening heart damage. The findings were published in Cell Reports Medicine. "Despite the prevalence of heart attacks, therapeutic options have stagnated over the last few decades," said Deb. "There are currently no medications specifically designed to make the heart heal or repair better after a heart attack."

The study demonstrated that a single dose of this antibody reduced scar tissue formation in mice and improved cardiac function. Four weeks post-heart attack simulation, only 5% of treated animals developed severe heart failure compared to 52% in the control group.

This therapy aims to enhance tissue repair directly, unlike current treatments that focus on damage prevention. The antibody targets cellular interactions affecting multiple cell types in the heart, including muscle cells and fibroblasts.

Initial preclinical studies suggest that this treatment decreases scar tissue without increasing rupture risk after a heart attack. However, Deb notes further research is needed to understand long-term effects on bone mass or calcification.

The team plans to move into clinical trials with an Investigational New Drug application submission to the FDA this winter, aiming for first-in-human studies by early 2025. These trials will test administering a single drug dose shortly after a heart attack.

Deb's team is also exploring applications for repairing other vital organs. "The mechanisms of tissue repair are broadly conserved across organs," said Deb. "Based on its effect on heart repair, this could represent a new class of tissue repair-enhancing drugs."

The therapy is covered by a patent held by the Regents of the University of California but has not yet been tested in humans or approved by the FDA.

Other contributors from UCLA include Shen Li, Bo Tao, Jijun Wan among others; Feiyang Ma from Northwestern University and Douglas B. Kitchen from Curia Global also contributed. The study was supported by various institutions including NIH and CIRM.