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Innovative research has led to the creation of a new intravenous therapy designed to be administered immediately following a heart attack, aimed at facilitating recovery and reducing the risk of heart failure.
This therapy enhances the immune response to aid in tissue restoration and ensures the survival of heart muscle cells post-incident. Experiments conducted on rat models demonstrated the therapy’s effectiveness lasting up to five weeks after injection.
A team of bioengineers from the University of California San Diego (UCSD) and chemists from Northwestern University spearheaded this study, which was published in the April 25 issue of the journal Advanced Materials.
“Addressing the risk of heart failure post-heart attack continues to represent a significant clinical challenge,” remarked Karen Christman, a leading author of the study and a professor in the Shu Chien-Gene Lay Department of Bioengineering at the UC San Diego Jacobs School of Engineering. “This therapy seeks to act rapidly after a heart attack to prevent the progression to heart failure.”
According to Nathan Gianneschi, the other lead author on the paper and a professor in the Department of Chemistry at Northwestern, the therapy holds promise for a wider range of medical applications.
“This therapeutic approach could be transformative for numerous conditions, ranging from macular degeneration to multiple sclerosis and even kidney diseases,” Gianneschi noted.
The therapy operates by inhibiting the interaction between two crucial proteins that play roles in the body’s stress and inflammatory responses. Activation of the protein Nrf2 enables cells to withstand damage caused by inflammation. However, KEAP1 binds to Nrf2, leading to its degradation. Following a heart attack, it is crucial to halt this degradation to allow for effective tissue recovery.
The platform developed, termed the protein-like polymer (PLP), resembles the Nrf2 protein. Once administered, it locates and binds to KEAP1, preventing it from degrading the actual Nrf2 protein.
In their experiments, researchers administered either the PLP platform or a saline solution to rat models after a heart attack, with the identities of the injections concealed from the team. Five weeks later, MRIs revealed that rats receiving the polymer exhibited improved cardiac function and notable healing in their heart muscle. Further analyses indicated increased expression of genes associated with tissue repair.
The authors view this study as a proof of concept. They intend to refine the design and dosage before proceeding to trials involving larger mammals.
“Proteins serve as the molecular engines essential for cellular processes, and disrupted protein interactions can lead to various human diseases,” Gianneschi explained. “Current drug options often struggle to penetrate cells or effectively engage with large target domains related to diseases. We aim to tackle these challenges from a fresh perspective.”
The therapy was developed by Gianneschi during his tenure at UCSD, where he is currently an adjunct faculty member, continuing his work at Northwestern.
This research was supported by grants from the National Institutes of Health (NIH) through the National Heart, Lung, and Blood Institute (NHLBI). Gianneschi is a co-founder of Grove Biopharma, which holds licensing rights related to this study’s intellectual property, in which both Gianneschi and Christman are co-inventors. He also serves on the Scientific Advisory Board for Grove Biopharma.
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