Key result
Adult human primary cardiomyocytes overcome artificial and animal model limitations in preclinical cardiac drug testing.
Why the study?
Current preclinical drug development strategies have significant limitations in predicting human heart effects, allowing cardiotoxic drugs to escape detection or causing potential therapies to be abandoned due to false positive signals.
Adult human primary cardiomyocytes provide a highly translational preclinical model for accurately predicting drug-induced cardiotoxicity and discovering new therapies for cardiac diseases.
In preclinical drug development, accurate prediction of drug effects on the human heart is critically important, whether in the context of cardiovascular safety or for the purpose of modulating cardiac function to treat heart disease. Current strategies have significant limitations, whereby, cardiotoxic drugs can escape detection or potential life-saving therapies are abandoned due to false positive toxicity signals. Thus, new and more reliable translational approaches are urgently needed to help accelerate the rate of new therapy development. Renewed efforts in the recovery of human donor hearts for research and in cardiomyocyte isolation methods, are providing new opportunities for preclinical studies in adult primary cardiomyocytes. These cells exhibit the native physiological and pharmacological properties, overcoming the limitations presented by artificial cellular models, animal models and have great potential for providing an excellent tool for preclinical drug testing. Adult human primary cardiomyocytes have already shown utility in assessing drug-induced cardiotoxicity risk and helping in the identification of new treatments for cardiac diseases, such as heart failure and atrial fibrillation. Finally, strategies with actionable decision-making trees that rely on data derived from adult human primary cardiomyocytes will provide the holistic insights necessary to accurately predict human heart effects of drugs.
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Abi‐Gerges et al. (2019) conducted a review in Cardiovascular safety and heart disease. Adult human primary cardiomyocytes vs. Artificial cellular models and animal models was evaluated. Adult human primary cardiomyocytes provide a reliable translational approach for preclinical drug testing, overcoming limitations of artificial and animal models in predicting human heart effects.
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