Cardiotoxicity is a major concern to pharmaceutical industry and regulatory agencies. Drugs are continuously removed from the market because of their toxic effects. To avoid cardiovascular side effects, regulatory agencies generated guidelines describing preclinical investigations to be performed before initiating clinical trials. These tests are often labor intensive and are conducted during the late stage of drug discovery, causing severe financial losses in case of safety issues. Thus, the development of a High-Throughput assay to be conducted during the early phase of drug development will reduce the overall cost and risk of new drugs development. Vala Sciences Inc. proposes to develop a human iPS cell line with a selectable marker for cardiac lineage differentiation and luciferase expression. Human cardiomyocytes, derived by the engineered iPS cells, will be used in combination with an automatic Calcium Transient Image Cytometer (CTIC), to analyze calcium transients and ATP concentration in 384 well format plates. These parameters are altered when cardiomyocytes are exposed to compounds that are either arrhythmogenic or toxic. The assay will identify compounds potentially compromised by cardiac safety concerns, allowing screening in human rather than animal cells, and thus decreasing the risk of adverse events when the drugs are eventually used clinically .
