Prof Glenn King, Institute for Molecular Bioscience, The University of Queensland and Infensa Bioscience Translational Research Institute, Brisbane, Australia.
Deadly cures: a venom-inspired ASIC1a inhibitor for treating ischemic injuries of the heart and brain
Please contact Prof John McCafferty if you would like to arrange a meeting with Prof King.
Myocardial infarction (MI) and stroke account for 27% of global mortality, yet there are no drugs available to prevent the ischemic injury they cause to the heart and brain. The drop in tissue pH during stroke and MI activates acid-sensing ion channel 1a (ASIC1a), which in turn promotes programmed cell death pathways. We isolated a disulfide-rich spider-venom peptide (Hi1a) that inhibits ASIC1a with picomolar potency and exceptional selectivity [1]. Hi1a dramatically reduces infarct size and improves behavioural outcomes when administered after ischemic stroke in rats [1], improves functional recovery in rodent and pig models of MI [2,3], and radically improves donor heart recovery in rodent and pig models of heart transplantation [2,3]. Collectively, our data provide compelling evidence that ASIC1a is a novel target for drugs to reduce the burden of MI and stroke, and increase the pool of donor hearts for transplantation. With a view to clinical translation, we developed miniaturised cyclic-peptide versions of Hi1a and in 2022 founded the Brisbane-based biotech company Infensa Bioscience to advance clinical development of these ASIC1a inhibitors. Infensa has completed IND-enabling preclinical toxicology studies and GMP manufacture of their nominated drug candidate, and a Phase 1 clinical trial for MI and heart transplantation will begin in October 2025.
1. Chassagnon et al. (2017) Proceedings of the National Academy of Sciences USA 114:3750–3755
2. Redd et al. (2021) Circulation 144: 947–960
3. Redd et al. (2024) European Heart Journal 45: 1571–1574
