SBIR/STTR Award attributes
PROJECT SUMMARY ABSTRACT The most significant advance in the treatment of Myocardial InfarctionMIhas been reperfusion therapywhich must be applied immediately after the MI diagnosis has been madeDespite the thousands of studies on drug therapies designed to reduce the size of the MImost have failed in clinical trialsOur hypothesis is that a major reason why these drugs failed is that they must be administered before therapeutic cardiac catheterization is performedThis significantly limits their utility in the clinical settingThe current proposal is based on studies in the Adenylyl Cyclase typeACknock out mouse modelwhich is protected against myocardial ischemiaobesitydiabetes and has enhanced exercise capacity and lives longer than wild typeOur preliminary data demonstrate that pharmacological inhibitors of the ACenzyme have a unique advantage in that they reduce infarct size even when administered after coronary reperfusionWe have developed a novelmore potent and more selective ACinhibitorCwhich is particularly attractive because it is a potent non nucleoside adenine ACinhibitor and also is not toxicWe have a patent pending on Cand selected this compound for clinical development based on efficacypharmacology and safetyPreliminary data indicate that Ccan reduce infarct size when administered after reperfusion by more thanin a mouse MI modelThe goal of this proposal is to obtain proof of principle in micein Watanabe rabbits with atherosclerosis and in a large mammalian animal model for infarct sizecardiac function and complete IND enabling pharmacologyADME and toxicology studies PROJECT NARRATIVE Despite the advances in the treatment of Acute MI and Heart FailureHFover the past several decadesthese diseases are the most significant health concerns in the U SThe most important therapy is to open the occluded coronary artery by catheterization when the patient with MI enters the hospitalThe goal of this research is to develop a new drug that when administered after the artery is opened reduces damage and helps to preserve recovery of myocardial functionprotecting against the development of heart failure
