Growth factor therapy for cardiac repair: an overview of recent advances and future directions.

Heart disease represents a significant public health burden and is associated with considerable morbidity and mortality at the level of the individual. Current therapies for pathologies such as myocardial infarction, cardiomyopathy and heart failure are unable to repair damaged tissue to an extent that provides restoration of function approaching that of the pre-diseased state. Novel approaches to repair and regenerate the injured heart include cell therapy and the use of exogenous factors. Improved understanding of the role of growth factors in endogenous cardiac repair processes has motivated the investigation of their potential as therapeutic agents for cardiac pathology. Despite the disappointing performance of other growth factors in historical clinical trials, insulin-like growth factor 1 (IGF-1), neuregulin and platelet-derived growth factor (PDGF) have recently emerged as new candidate therapies. These growth factors elicit tissue repair through anti-apoptotic, pro-angiogenic and fibrosis-modulating mechanisms and have produced clinically significant functional improvement in preclinical studies. Early human trials suggest that IGF-1 and neuregulin are well tolerated and yield dose-dependent benefit, warranting progression to later phase studies. However, outstanding challenges such as short growth factor serum half-life and insufficient target-organ specificity currently necessitate the development of novel delivery strategies.