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Cardiotoxicity is among of the most common causes for clinical and post-market drug attrition. Examples of that are the withdrawal of Rofecoxib and Cisapride. Thus, an early (and predictive) assessment of drug-induced cardiotoxicity is essential during the drug development process
In a recent article, we show a high correlation between zebrafish larvae and clinical cardiotoxic data (PPV=86%;NPV=57%). This predictive values are in line with those obtained when using the dog model, the gold-standard in vivo model for cardiotoxicy prediction (1). In line with that, the comparison between the zebrafish larvae and the in vitro hERG models revealed a strong correlation (R2 = 0.714), indicating zebrafish as a strong alternative model for drug cardiotoxicity assessment (2).
ZeCardio is a fully automatized drug-screening platform that integrates image acquisition and analysis tools developed by ZeClinics. The platform allows the quantification of relevant cardiovascular parameters in zebrafish larvae, allowing the prediction of drug-induced cardiovascular liabilities in humans, in a fast and cost-effective manner.
1. Dyballa S et al. 2019. Comparison of Zebrafish Larvae and hiPSC Cardiomyocytes for Predicting Drug-Induced Cardiotoxicity in Humans. Toxicological Sciences
2. Dingsheng Wen, Aiming Liu, Feng Chen, Julin Yang and Renke Dai. 2012. Validation of visualized transgenic zebrafish as a high throughput model to assay Bradycardia related cardio toxicity risk candidates. Journal of App. Tox.
3. Shin JT, Pomerantsev EV, Mably JD, MacRae CA. 2010. High-resolution cardiovascular function confirms functional orthology of myocardial contractility pathways in zebrafish. Physiol. Genomics.
4. Patricia McGrath and Chun-Qi Li. 2008. Zebrafish: a predictive model for assessing drug-induced toxicity. Drug Discovery Today.
5. Milan DJ, Peterson TA, Ruskin JN, Peterson RT, MacRae CA. 2003. Drugs that induce repolarization abnormalities cause bradycardia in zebrafish. Circulation.