Myocardial delivery of MMP inhibiting hydrogels

ABSTRACTOvermillion people in the United States currently suffer from heart failure caused by a myocardial infarctionMIand more thansurvivable MIs occur each yearThese troubling statistics amount to an economic burden of over $billion annuallyCurrent clinical treatments for MI include coronary stents and bypass surgeries to overcome the blocked artery and pharmacologic prescription to lessen the workload of the injured heartUnfortunately these treatments do little to alter the tissue remodeling process initiated after coronary artery occlusionand progression to heart failure is commonMatrix metalloproteinasesMMPsare a class of tissue degrading enzymes that contribute to adverse tissue remodeling post MIWhile systemic administration of MMP inhibitors has shown beneficial effects in preclinical animal modelsthis approach was limited in patients due to off target effects of the inhibitorsTo overcome these limitations we have recently reported the local delivery of an inhibitor to MMPsTIMPto the infarct using injectable hydrogelsThe injectable hydrogels were designed to dose TIMPrelease in proportion to MMP activity within the myocardium in order to address concerns of MMP expression heterogeneities in patients post MIThis novel delivery technology significantly attenuated adverse LV remodeling in a preclinicallarge animal model of MIwhich was published in the journal Nature MaterialsIn additionthe technology has been protected by an issued patent and several additional patent applications have been filedFurtherProhibixLLC was founded by the inventors to commercialize the technologyThe objective of the proposed work is to further develop the bioresponsive hydrogel technology into a translatable catheter delivered productwith the overall goal of attenuating the progression towards heart failure in MI patientsFirstwe will develop a formulation that can be safely passed through a clinically available and validated catheterSecondwe will demonstrate that the formulation can be reliably injected into the myocardium via a percutaneous catheterizationCompletion of this proposal will lay the groundwork for safety and efficacy studies of the catheter deliver hydrogels as a follow up Phase II investigationFurtherthis work will strengthen interest from industry partners as it opens the therapy to treating a large and growing patient population who suffer an MI NARRATIVE The progression to heart failure following a myocardial infarctionMIis a major public health concernCare for patients with heart failure puts a large economic burden on the healthcare system and requires large commitments from caregiversProhibixLLC is developing a novel approach to attenuate the progression to heart failure following MIwhich will give cardiologists a new tool to treat MI and decrease the burden of MI by being safeeffective and easy to use alongside current treatment procedures