[caption id="attachment_16664" align="alignleft" width="300"] Human cardiomyocyte-derived induced pluripotent stem cells recapitulate the phenotype and function expected of human tissue. The image shows CDI’s iCell Cardiomyocytes staining for cytoskeleton proteins and illustrates the subcellular sarcomeric localization and structure necessary for contraction.[/caption]

Therapeutics fail during the discovery and development cycles for many reasons, such as bioavailability, efficacy, or toxicity. Predicting low instances of toxicity, which may only emerge late in development, in clinical trials, or even after the compound is on the market, is very challenging.

The need to identify low instances of toxicity earlier, exemplified by examples such as the CCR5 inhibitor RO5657 and the CD28-specific mAb TGN1412, drives advancements in predictive toxicity assays. Thought leaders meet regularly to discuss state-of-the-art research. For example, they recently convened at the International Summit on Toxicology and Applied Pharmacology, which took place in Chicago.

One of the issues taken up at this event was the application of induced pluripotent stem cells (iPSCs). This approach was considered by Roche, in collaboration with Cellular Dynamics International (CDI), after the pharma giant’s CCR5 inhibitor RO5657 was dropped. Although RO5657 progressed through hERG and preclinical cardiotoxicity assessment, it was ultimately dropped due to severe cardiotoxicity in primates.