Therapeutic to Reduce Acute Inflammation Following Cardiac Ischemia

DESCRIPTION (provided by applicant): Reperfusion injury (Rl) is a serious life-threatening inflammatory process of unknown etiology that occurs when blood flow is returned to an ischemic tissue, for example heart muscle following a heart attack or cardiac surgery. The restoration of blood flow to previously ischemic tissue results in cardiac inflammation and tissue damage. Studies at Declmmune have now proven the pivotal role natural antibodies play in the initiation of Rl. The company has isolated the first pathogenic natural antibody in a mouse model, identified the specific ischemic antigen target of this antibody, and prepared peptide mimetopes. These peptides, when administered prior to or shortly after ischemia, block reperfusion injury to intestine and hind limb muscle in mice and prevent myocardial infarction following ischemia and reperfusion in the mouse heart. The aim of this grant is to determine if the specificity of the natural antibody and ischemic antigen identified in mice is conserved in humans. The research design will utilize the reagents and animal models that have been developed in the mouse studies and apply them to the evaluation of human tissue and blood samples. A successful outcome will lead to the development of a therapeutic compound to be used to prevent acute inflammation following cardiac ischemia. The company anticipates that its first product will be either a peptide or a blocking agent (e.g., antibody, aptimer, or other binder) that will be administered to patients prior to open heart surgery. More than 690,000 open heart procedures are performed in the US annually. Approximately 12% of these patients die or have a heart attack within 6 months of surgery and Rl is a major cause. In addition the compound could have significant potential in treating patients following myocardial infarction or stroke.