ZeTox

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icon-cardio-tox CardioTox

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. 

Method description and readouts

Figure: The platform has been validated on 92 compounds, with known target and cardiotoxic activity in humans, to provide a comprehensive comparison of drug-induced cardiotoxicity in human with data from zebrafish larvae. (1)

Internal validation data

References

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.