Dana Kelly   Posted in News    Oct 14th, 2016

Stemina to Present at Use of Cardiomyocytes for the Assessment of Proarrhythmic Risk Conference October 25-26

Jessica Palmer will present a poster entitled “Development of a Biomarker-Based Cardiotoxicity Assay using Human Pluripotent Stem Cell-Derived Cardiomyocytes” at the upcoming Use of Cardiomyocytes for the Assessment of Proarrhythmic Risk Conference in Arlington, Virginia. 

Poster Abstract: 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. Stemina is developing a novel biomarker-based assay for evaluating the cardiotoxicity potential of a compound based on the human induced pluripotent stem cell (hiPSC)-derived cardiomyocyte metabolic signature. The ultimate goal of this work is to develop an assay that is able to discriminate between structural and functional cardiotoxicity that could be used in conjunction with CiPA to provide a more comprehensive evaluation of a compound’s cardiotoxicity potential. Pilot studies conducted with a set of 24 pharmaceutical agents of known cardiotoxicity demonstrated the potential to separate cardiotoxins from non-toxins using a metabolomics-based assay with 93% accuracy. This work provided proof-of-concept that changes in metabolism can be used to predict cardiotoxicty in vitro.

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