Toxicity is a major problem in drug development and there is no convenient in vivo model for assessing effects of compounds on cardiac function. To reduce the number of compounds that progress to laborious and costly late stage animal testing, this SBIR proposes to develop zebrafish as an in vivo pre-clinical model to assess cardiac toxicity of potential drug candidates. This SBIR will assess embryogenesis and patterning, as well as cardiotoxicity effects after drug treatment. Zebrafish has several advantages over existing whole animal models used in cardiotoxicity screening. In contrast to other vertebrate models, zebrafish develops rapidly, and the heart is fully formed and functioning at 36 hours post fertilization. In addition, zebrafish is transparent, facilitating visual observation and analysis. Zebrafish are also permeable to small molecules, which can be dissolved and delivered directly in fish water. Zebrafish drug screens can serve as an intermediate step between cell-based and mammalian testing, streamlining the drug development timeline.
