Researchers have developed a new therapy that can be injected intravenously right after a heart attack to promote healing and prevent heart failure. The therapy both prompts the immune system to encourage tissue repair and promotes survival of heart muscle cells after a heart attack. Researchers tested the therapy in rats and showed that it is effective up to five weeks after injection. The research team, led by bioengineers at the University of California San Diego and chemists at Northwestern University, published their findings in the April 25 issue of the journal Advanced Materials. The therapy could have broader applications, said Nathan Gianneschi, the paper’s other corresponding author and a professor in the Department of Chemistry at Northwestern.
The platform aims to block the interaction of two key proteins that intervene in the body’s response to stress and inflammation. When the cellular transcription factor Nrf2 is activated, cells resist the degradation brought on by inflammation. But KEAP1 binds with Nrf2 to interfere with its activation and committ it toward degradation. After a heart attack, this process of degradation has to be stopped so that tissues can health better. The protein-like polymer, or PLP, platform is made from a polymer that mimics Nrf2. Once injected intravenously, it finds KEAP1 and binds to it, preventing it from binding to the actual Nrf2 protein and degrading it. Researchers injected rat models after a heart attack with either the PLP platform or a saline solution.
The team was blinded to which animals received the polymer or saline. After five weeks, the rodents underwent MRIs while sedated. The animals injected with the polymer showed better cardiac function and significantly more healing in their heart muscle tissue. Other tests also showed that genes that promote healing of tissues were expressed more. Researchers describe the study as a proof of concept. Before moving on to tests in larger mammals, they want to optimize the design and dosage, and conduct further analysis. Proteins are the molecular machines that drive all essential cellular function, and dysregulated intracellular protein-protein interactions are the cause of many human diseases.
THey can be modulated naturally by drugs or natural substances. Nrf2 activators are widely known and are employed by scientists to study cellular antioxidant defences after trauma or injury (es. for brain, kidney, etc.). HOwever, existing drug modalities are scarcely able to penetrate cells or cannot effectively engage these large disease target domains. The therapy method was developed by Dr. Gianneschi, while he was a faculty member at UC San Diego, where he is now an adjunct faculty. He continued working on the technology at Northwestern and became a co-founder of Grove Biopharma, which licensed intellectual property related to the study. Drs Gianneschi and Christman are co-inventors on that same intellectual property.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Scientific references
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