Current interventional treatment of acute myocardial infarction (AMI) focused on re-establishing cardiac reperfusion has significantly improved clinical outcome by reducing infarct size and mortality due to cardiac ischemia.It is now recognized that events triggered at reperfusion also result in cell death and may account for as much as 50% of the infarct volume, this being termed ischemia-reperfusion injury (IRI). Mitochondrial permeability transition pore (mPTP) opening appears to be a responsible for IRI and a recent small clinical trial with cyclosporine A shows that it is a feasible target for the development of new therapies to treat it. Since total infarct size is a major determinant of a patients risk to develop heart failure, treating IRI is expected to further reduce morbidity, mortality and the need for regenerative medicine following cardiac ischemia. By harnessing a multi-disciplinary consortium of clinical and basic scientists along with four SMEs, MitoCare brings state-of-the art expertise together to 1) better understand IRI pathophysiology and factors directly or indirectly influencing patient’s recovery or response to treatment; 2) investigate the translational usefulness of preclinical models; and 3) compare selected treatments. These objectives will be reached through the following work plan: A) a medium-scale phase II clinical study will evaluate the efficacy of a novel complementary therapy to PCI, the new mPTP modulator TRO40303, while at the same time 1) perform extensive sampling from subjects in the study for analysis of standard and emerging biomarkers; 2) identify confounding factors influencing patients’ outcomes. B) Parallel investigations in preclinical in vitro and in vivo AMI models. C) Statistical analysis of data from clinical and preclinical studies, to identify better diagnostic and prognostic endpoints in man and assess predictive utility of preclinical models.
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Funding SchemeCP-FP - Small or medium-scale focused research project
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