Preclinical Development of Gene Therapy: The Effects of Urocortin 2 and Urocortin 3 Gene Transfer in Murine Models of Heart Failure and Diabetes

Cardiovascular disease is leading cause of death in the western societies, with dismal outlook even upon optimal treatment which underlines the necessity of better therapies. Urocortin-2 and urocortin-3 intravenous infusion improved heart function in humans. However, constant administration of these proteins is required for chronic treatment due to their short half-life (few minutes), a problem that could be solved by gene transfer of those peptides. This work demonstrates that one intravenous injection of adeno-associated virus encoding urocortin-2 or urocortin-3 increases cardiac function in mice. Furthermore, urocortin-2 gene transfer increased insulin sensitivity in mice. These findings support urocortin-2 and urocortin-3 gene transfer as potential treatment for heart failure and diabetes.