Myocardial infarction (MI or “heart attack”) is a major cause of death and disability worldwide. In patients with MI, the treatment of choice for reducing acute myocardial ischemic injury and limiting MI size is timely and effective myocardial reperfusion using either thombolytic therapy or primary percutaneous coronary intervention. However, the process of reperfusion can itself induce cardiomyocyte death, known as myocardial reperfusion injury, for which there is still no effective therapy.
Investigators at Baker IDI and Monash have discovered that signalling by the Formyl Peptide Receptor-1 (FPR1) provides cardioprotection in the context of ischaemia-reperfusion injury (IRI), and further that this signalling shows evidence of bias. The investigators have identified a small-molecule drug candidate which acts as an FPR1 agonist with the requisite bias and shown this candidate does indeed provide cardioprotection in well-characterised animal models of IRI, abrogating cardiomyocyte necrosis, infarct size, left ventricular (LV) inflammation, remodelling and LV contractile dysfunction. Of clinical relevance, cardioprotection is preserved even when treatment is delayed until reperfusion. These compelling observations provide the basis for targeted development of biased, small molecule FPR agonists as a novel strategy for treating MI.
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