Heart regeneration: Opportunities and challenges for drug discovery with novel chemical and therapeutic methods or agents

Abstract

Following a heart attack, more than a billion cardiac muscle cells (cardiomyocytes) can be killed, leading to heart failure and sudden death. Much research in this area is now focused on the regeneration of heart tissue through differentiation of stem cells, proliferation of existing cardiomyocytes and cardiac progenitor cells, and reprogramming of fibroblasts into cardiomyocytes. Different chemical modalities (i.e. methods or agents), ranging from small molecules and RNA approaches (including both microRNA and anti-microRNA) to modified peptides and proteins, are showing potential to meet this medical need. In this Review, we outline the recent advances in these areas and describe both the modality and progress, including novel screening strategies to identify hits, and the upcoming challenges and opportunities to develop these hits into pharmaceuticals, at which chemistry plays a key role. Small molecules, RNA approaches, modified peptides, and proteins are promising candidates for the regeneration of heart tissue through differentiation of stem cells, proliferation of existing cardiomyocytes and cardiac progenitor cells, and cell reprogramming to cardiomyocytes. Recent advances, including novel screening strategies, and the upcoming challenges and opportunities to develop these hits into pharmaceuticals are summarized. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.