Discussion

Cardiotoxicity is a major cause of drug withdrawal from the market and attrition during drug development. Drug-induced cardiotoxicity results from both functional effects and structural changes to the heart. Currently, in vitro screens to identify subtypes of functional cardiotoxicity in new drug candidates rely on over-expressing cell lines and primary cells, the latter of which is not amendable to high through-put screening. Additionally, screens for drugs that cause structural cardiotoxicity have not been developed due to poorly defined molecular mechanisms and inadequate in vitro models. Advances in human and mouse, embryonic and induced pluripotent stem cell technology represents a new opportunity for assessing drug-induced cardiac safety and provides an opportunity for the development of physiologically relevant in vitro models. Our presentation will describe the utility of stem cell derived cardiomyocytes for the assessment of functional cardiotoxicity, using the FLIPR Tetra and IonOptix systems to detect functional cardiotoxic liabilities in candidate drugs. Additionally the development of complex 3D multicellular cardiovascular models will be discussed.