Ralf Kettenhofen, Ncardia, Köln, Germany
Drug development projects in the pharma industry are focused on efficacy screening for the target of interest. But often compounds fail due to safety issues in costly late-stage safety pharmacological studies. For that reason, high throughput sodium, calcium and hERG ion channel binding assays and automated patch clamp of recombinant cell lines expressing the human ion channels were implemented.
Still a comprehensive in vitro cardiomyocyte model is missing in order to bridge the gap to low throughput ex vivo and in vivo studies.
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSCM) are currently in the validation process of the comprehensive in vitro proarrhythmia (CiPA) initiative and have already been proven to predict the effects of clinically relevant compounds with very high sensitivity and specificity.
In this presentation, I will show how hiPSCMs are used in high throughput capable fluorescent calcium sensitive dye assays to optimize lead compounds in SAR studies in regards of cardiac safety and how sped up the drug development process bridging the gap to late stage safety studies.