Researchers have developed an innovative injectable therapy that could transform how heart attacks are treated and potentially prevent patients from developing heart failure. Administered intravenously shortly after a heart attack, the treatment helps the heart heal by activating the body’s immune system to support tissue repair and protect heart muscle cells from further damage. Remarkably, the therapy remained effective even when administered up to five weeks after the heart attack in preclinical trials.

The study, published in the April 25 issue of Advanced Materials, was conducted by a team of bioengineers from the University of California San Diego and chemists from Northwestern University. Their approach directly addresses a major clinical challenge: how to intervene early to stop the progression from heart attack to heart failure. According to Karen Christman, one of the study’s senior authors and a professor at UC San Diego, preventing heart failure remains a critical unmet medical need. She emphasized that this therapy is designed to fill that gap by acting as soon as possible after a heart attack to protect and preserve heart function.

The therapy works by targeting a key molecular interaction that disrupts cellular repair mechanisms following a heart attack. Specifically, it interferes with the activity of two proteins: Nrf2 and KEAP1. Nrf2 plays a protective role by helping cells resist inflammation-induced damage, but it is typically degraded by KEAP1, especially after a cardiac event. The therapy uses a specially engineered protein-like polymer (PLP) that mimics Nrf2. When injected, the PLP binds to KEAP1, preventing it from degrading natural Nrf2. This allows the heart tissue to heal more effectively.

In trials on rats, researchers administered the therapy intravenously after inducing heart attacks. The study was blinded, with some animals receiving a saline solution and others the PLP therapy. Five weeks later, MRI scans revealed that the rats treated with the polymer had significantly better heart function and less tissue damage compared to those that received saline. High-resolution imaging confirmed that the PLP-treated hearts showed much smaller regions of cell damage. Additional tests indicated that genes responsible for tissue repair were more actively expressed in the treated animals.

Nathan Gianneschi, a chemistry professor at Northwestern and co-author of the study, noted that the implications of this therapeutic platform extend well beyond cardiology. Because it targets protein-protein interactions within cells, a mechanism that underlies many serious conditions, the same approach could be adapted to treat diseases such as macular degeneration, multiple sclerosis, and kidney disease.

The researchers view this study as a proof of concept. Before advancing to tests in larger mammals or humans, they plan to optimize the therapy’s formulation and dosage, and conduct further safety and efficacy studies. Gianneschi explained that many diseases arise from dysfunctional protein interactions that current drugs cannot reach. By designing therapies that can enter cells and engage these complex molecular targets, the team is exploring a new frontier in drug development.

This therapy represents a promising shift in how post-heart attack care could evolve, not only offering hope to cardiac patients but also paving the way for a broader class of treatments for complex, hard-to-treat diseases.

By Impact Lab