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Cross-species translation of drug-induced electrophysiological response in cardiac myocytes

Stefano Morotti, PhD.
Assistant Professor at University of California Davis

Animal experimentation is key in the evaluation of cardiac efficacy and safety of novel therapeutic compounds. However, inter-species differences in the mechanisms regulating excitation-contraction coupling can limit the translation of experimental findings from animal models to human physiology, and undermine the assessment of drugs’ efficacy and safety. By combining computational modeling and statistical analysis, we built a suite of translators for quantitatively mapping electrophysiological responses in ventricular myocytes across species, and then tested them against experimental data describing the response to various stimuli, including ion channel block and β-adrenergic challenge. Our work demonstrates that this approach is well suited to predicting the effects of perturbations across different species, and suggests its integration into mechanistic studies and drug development pipelines.