MicroRNA302 for post-MI cardiac regeneration

Although up toof patients survive hospitalization following MImany of these patients will develop chronic heart failure due to extensive damage to heart muscleresulting inmortality at five years post MI and a huge economic burdenOne chief cause of heart failure is cardiomyocyte death post MIwhich is part of the left ventricular remodeling process that leads to replacement of functional tissue with a densefibrotic scarDue to the inability of cardiomyocytes to effectively re enter the cell cycle and proliferatecontrolled induction of cardiomyocyte proliferation is an emerging and important goal for therapies aimed at improving outcomes after MIMurine studies have shown that cardiac administration if microRNAmiRa natural inhibitor of Hippo signalingin a gel formulation allowing for release of the RNA overweek leads to vastly decreased scar size and improved cardiac function following ischemia reperfusionThis approach to cardiac regeneration is compelling by combining the simplicity of local administration of a single molecule at a single timepoint with the ability of miRto profoundlybut transiently affect the developmental state of cardiomyocytesunder the action of miRin situ adult cardiomyocytes de differentiate to an earlierproliferative stateAs miRis rapidly degraded once released from the formulationthe cells revert to adultfully functional cardiomyocytes after an initial phase of proliferationThusby interfering with a series of coordinated pathwaysmiRconfers the cardiac regenerative property of lower vertebratese gzebrafishto the murine heartProlifagen is developing a microRNA mimicmiRadministered as a single intracardiac injection in a gel formulationto induce cardiac regeneration after myocardial infarctMIand thus prevent cardiac remodeling and heart failureOur SBIR phase I proposal will test the hypothesis that local miRhydrogel treatment is able to drive cardiomyocyte proliferation covering the extended area of cardiac damage in a pig model of ischemiareperfusionas a proof of concept enabling clinical trial decisionIn additionexploration of the proliferative response attimepoints after myocardial infarction will allow to best define the optimal patient population for clinical developmentBy reducing the numberof patients with heart failure subsequent to myocardial infarctiona successful product will have a huge public health impactkeeping patients independent and avoiding hospitalizationscostly heart transplants and death Prolifagen LLC is developing a treatment intended to regenerate cardiac tissue after myocardial infarction based on intracardiac administration of mira microRNA acting through inhibition of the Hippo pathwayformulated in a gel allowing for sustained release overweekThis regenerative treatment is intended to prevent heart failure following myocardial infarction