New Models for Assessing Effects of Contractility

描述（由申请人提供）：药物毒性是停药的主要原因，也是临床试验延迟或失败的主要原因。最近万络，一种广泛使用的抗关节炎药物，由于增加心脏病发作和中风的风险而从市场上撤下。其他药物，如特非那定，格帕沙星和西沙必利也因严重的心脏毒性而从美国市场上撤下。药物心脏毒性对患者安全和生物制药行业的财务稳定都构成严重威胁。本研究的目的是建立一个体内临床前模型，通过测量心脏血容量和血压来评估药物治疗后的心脏收缩力。这种斑马鱼筛选将简化药物开发时间线，优先考虑动物试验的候选药物，并减少哺乳动物研究的不必要成本。这种方便的动物模型将作为基于细胞的评估和传统动物试验之间的中间步骤。公共卫生相关性：本研究的目的是建立一个体内临床前模型，通过测量心脏血容量和血压来评估药物治疗后的心脏收缩力。

DESCRIPTION (provided by applicant): Cardiotoxicity is the leading cause of drug withdrawal, and is a major reason for delays or failure during clinical trials. Recently Vioxx, a widely used anti-arthritic drug, was removed from the market due to increased risk of heart attack and stroke. Other drugs such as terfenadine, grepafloxacin and cisapride were also removed from the U.S. market due to serious cardiac toxicity. Drug cardiotoxicity represents a serious threat both to patient safety and to the financial stability of the biopharmaceutical industry. The aim of this research is to establish zebrafish as an in vivo preclinical model to assess cardiac contractility after drug treatment by measuring cardiac blood volume and blood pressure. This zebrafish screen will streamline the drug development time-line, prioritize drug candidates for animal testing, and reduce unnecessary costs for mammalian studies. This convenient animal model will serve as an intermediate step between cell-based evaluation and conventional animal testing. PUBLIC HEALTH RELEVANCE: The aim of this research is to establish zebrafish as an in vivo preclinical model to assess cardiac contractility after drug treatment by measuring cardiac blood volume and blood pressure.