LOW DOSE IGF1 FOR CARDIAC CYTOPROTECTION AND REPAIR FROM MOUSE TO MAN



Noel M. Caplice, M.D., Ph.D., University College Cork, Ireland

IGF1 is an endogenous pro-survival peptide within the adult heart. We have previously identified low dose IGF1 (LD-IGF1) as a potent paracrine factor secreted from endothelial progenitor cells known to facilitate cardiac repair post myocardial infarction (MI). We have also demonstrated in a murine MI model that low concentrations of IGF1 secreted via modified RNA promote a cardiac survival pathway in the 24 -48 hours post therapy. Moreover, in a porcine MI model of human scale we have shown that cognate IGF1 receptor signalling occurs within 30 mins of intracoronary injection of LD-IGF1 in the setting of ischemia-reperfusion. Specific receptor activation promotes acute cardiomyocyte survival in the infarct and border zones with medium term improvement in ventricular function, cardiac remodelling and scar formation. More recently in a phase I/II randomised placebo controlled clinical trial we have shown that specific doses of LD-IGF1 are safe and have a beneficial effect on cardiac remodelling assessed by MRI in the setting of large ST elevation myocardial infarcts associated with moderate LV dysfunction. This latter effect is most likely driven by acute reduction in infarct size and limitation of ventricular chamber expansion.