Development of a Targeted Biomarker Assay to Predict Cardiotoxicity Potential Using Metabolomics and Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes [ACT 2017]
Presented at the American College of Toxicology’s 38th Annual Meeting in Palm Springs, California in November 2017 by Stemina’s Associate Director of Toxicology, Jessica Palmer.
Cardiac safety is one of the leading causes of late-stage compound attrition in the pharmaceutical industry and accounts for 28% of the safety related withdrawals of FDA-approved drugs from the market. Current cardiac safety preclinical evaluations are heavily focused on approximately 3-7 main ion channels involved in maintaining the cardiac action potential; however, over 70 different types of ion channels are expressed in the heart and participate in the overall cardiac current.
These safety testing methods overemphasize electrophysiological assessment of cardiotoxicity and fail to evaluate cardiomyopathy and other forms of structural cardiotoxicity. Metabolic perturbations are one of the primary mechanisms underlying the cardiotoxicity elicited by pharmaceuticals.
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