Des-asp angiotensin 1 (DAA-1) is a potent endogenous cardiovasculo-protective peptide generated from angiotensin 1 by a novel aminopeptidase. DAA-1 given both iv and po has sub-micromolar protective activity in a number of cardiac and renal pathophysiology. These activities are mediated by a unique angiotensin 1 receptor subtype. Based on the novel proprietary activities of DAA-1 and its limited toxicity, the overall goal of the present project is to expand the preclinical studies of DAA-1 to support submission of an IND. Clinical need and preclinical animal studies of DAA-1 support its initial use in the context of myocardial infarction-reperfusion injury. In Phase I the activity of DAA-1 will be compared to ACE inhibition and ARB drugs using a rat cardiac reperfusion model. This will be followed by a comparison of the drugs versus DAA-1 in a porcine cardiac reperfusion model. Phase II goals include preparation of GMP grade DAA-1, expansion of preclinical toxicology studies, and validation of assays of DAA-1 in preparation for submission of an IND application. Because DAA-1 binds a novel, validated target, this molecule is expected to have significant therapeutic potential in cardiovascular medicine.
