One of the main R&D focus areas in ZeClinics has been the development and validation of the most advanced tool currently available for cardiovascular analysis in Zebrafish: ZeCardio®. This technology/methodology combines robotic microfluidic and imaging equipment, together with proprietary software developed in-house that permits to analyze the impact of drugs and genetic conditions on cardiac – heart rate, arrhythmia, AV Blockage and ejection fraction – and vascular function – blood flow and vasodilation/constriction – in the zebrafish larvae and its validation has been recently published.
The aim of the ZeCardio® platform is to perform high-throughput screening (HTS) of large libraries in live organisms for cardiovascular impact assessment. Additionally, ZeCardio® is very useful for performing genetic target validation studies and understanding the MoA of discovered molecules. At full capacity, ZeCardio® can screen 90 molecules per week or 3 genetic conditions. This platform, combined with ZeCardioTx scientific expertise, will serve as a pedestal for the identification of new druggable targets and molecules with further potential for unmet human cardiovascular medical needs.
Drug discovery relies on costly, time-consuming and not always translational research with mammals to advance a molecule toward clinical phases. New research models are emerging to streamline drug discovery and allow better correspondence between preclinical and clinical data. Among them, zebrafish stands as a powerful model for disease target validation and drug discovery. 35,000 articles on zebrafish research have been published during the last 20 years; over 10,000 related to the validation of the model for understanding human disease and its use for discovering new drugs, both from a safety and efficacy standpoints. Relevantly, 200 drug discovery pipelines have been reported using zebrafish; from them, around 60 drugs are in clinical phases. The increasing use of zebrafish in drug discovery is due to its significant experimental and translational advantages. Zebrafish genome is fully sequenced and can easily be manipulated using well-established gene editing approaches. Hundreds of embryos can be produced at once and zebrafish larvae are permeable to drugs; thus, multiple molecules can be screened in parallel and statistical significance can be achieved at a lower cost than by using rodents. Finally, zebrafish transparency allows internal organs to be easily observed via microscopy. In summary, homology with human physiology, genetics, and metabolism allows discovering druggable targets and predicting drug toxicity, efficacy, and mechanism of action in a fast, cost-effective and biologically robust (MacRae and Peterson, 2015).
Regarding cardiovascular research, zebrafish and human hearts share remarkable similarities in terms of development, genetics, physiology, ECG patterns, disease phenotypes and drug responses. That makes zebrafish a highly predictive model for preclinical drug assays in the cardiovascular area (Asnani and Peterson, 2014).