Article Impact Level: HIGH Data Quality: STRONG Summary of Advanced Materials, 2417885. https://doi.org/10.1002/adma.202417885 Dr. Joshua M. Mesfin et al.
Points
- Researchers have developed a new therapy using an Nrf2-mimetic polymer to prevent heart failure and promote repair after myocardial infarction. The therapy targets oxidative stress through disruption of the Keap1/Nrf2 interaction.
- In preclinical trials, intravenous therapy administration shortly after MI in rats improved cardiac function and reduced oxidative damage through immunomodulatory and angiogenic effects.
- MRI scans and gene expression analysis showed that a single dose of the polymer significantly enhanced heart tissue recovery and upregulated genes related to healing.
- This approach holds promise not only for heart attacks but also for other diseases involving oxidative stress, such as macular degeneration, multiple sclerosis, and kidney disease.
- Researchers plan to continue optimizing the dosage and evaluating long-term efficacy to expand the potential clinical applications of this novel therapy.
Summary
A novel therapeutic approach targeting myocardial infarction (MI) has been developed to prevent heart failure and promote tissue repair. The therapy inhibits the Keap1/Nrf2 protein-protein interaction, which regulates the oxidative stress response after MI. The research team utilized a Nrf2-mimetic protein-like polymer (PLP), disrupting the interaction between Keap1 and Nrf2. This disruption leads to Nrf2 activation, which protects heart cells from oxidative stress. The PLP platform offers stability in vivo, strong binding affinity, and potent bioactivity, showing significant promise for treating MI-induced cardiac damage.
In preclinical trials, the PLP therapy was administered intravenously to rats at a single-digit mg/kg dose within a few hours post-MI. The results showed that the therapy improved cardiac function by promoting immunomodulatory, anti-apoptotic, and angiogenic responses. Specifically, single-dose PLP administration reduced the effects of oxidative stress, significantly enhancing tissue repair and improving overall heart function. The therapy led to substantial recovery of heart muscle tissue as evidenced by MRIs conducted five weeks after injection. Additionally, PLP-treated animals exhibited upregulation of healing-related genes. These outcomes suggest that the therapy provides a robust intervention for heart failure prevention post-MI.
The study’s findings have broad implications for not only MI but also other conditions driven by oxidative stress, such as macular degeneration, multiple sclerosis, and kidney disease. The researchers highlight the unique advantage of their PLP therapy platform, which successfully prevents the degradation of Nrf2, a crucial protein in cellular stress response. This research represents a significant advancement in MI treatment, with the potential for broader applications in other diseases characterized by oxidative stress-driven tissue damage. Further optimization and testing are planned to refine the dosage and improve therapeutic efficacy.
Link to the article: https://advanced.onlinelibrary.wiley.com/doi/10.1002/adma.202417885
References Mesfin, J. M., Carrow, K. P., Chen, A., Hopps, M. P., Holm, J. J., Lyons, Q. P., Nguyen, M. B., Hunter, J. D., Magassa, A., Wong, E. G., Reimold, K., Paleti, S. N., Gardner, E., Thompson, M. P., Luo, C. G., Zhang, X., Christman, K. L., & Gianneschi, N. C. (2025). Proteinālike polymers targeting keap1/nrf2 as therapeutics for myocardial infarction. Advanced Materials, 2417885. https://doi.org/10.1002/adma.202417885
