Cardiotoxicity Drug Screening Using Zebrafish

利用斑马鱼进行心脏毒性药物筛选

• 批准号: 6835553
• 负责人: Chuenlei Parng
• 金额: $ 13.98万
• 依托单位: PHYLONIX PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6835553
• 关键词: cardiotoxin; cardiovascular function; cost effectiveness; drug adverse effect; drug screening /evaluation; embryo /fetus drug adverse effect; embryogenesis; heart circulation; heart contraction; heart rate; heart rhythm; light microscopy; pharmacokinetics; zebrafish

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）： 毒性是药物开发中的主要问题，体内模型没有方便的用于评估化合物对心脏功能的影响。为了减少发展为费力且昂贵的晚期动物测试的化合物数量，该SBIR建议将斑马鱼发展为体内临床前模型，以评估潜在候选药物的心脏毒性。该SBIR将评估药物治疗后的胚胎发生和模式，以及心脏毒性作用。斑马鱼比用于心脏毒性筛查的现有整个动物模型具有多个优点。与其他脊椎动物模型相反，斑马鱼的发展迅速，心脏在受精后36小时充分形成并发挥作用。此外，斑马鱼是透明的，促进了视觉观察和分析。斑马鱼也可渗透到小分子，这些分子可以溶解并直接在鱼类水中递送。斑马鱼药物筛查可以作为基于细胞和哺乳动物测试之间的中间步骤，从而简化了药物发育时间表。