ENZYME IMMOBILIZATION FOR REMOVAL OF TOXIC METABOLITES

用于去除有毒代谢物的酶固定化

• 批准号: 3507414
• 负责人: Patrick E Guire
• 金额: $ 19.65万
• 依托单位: SURMODICS, INC.
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-30 至 1992-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3507414
• 关键词: arginase; clinical biomedical equipment; enzyme therapy; extracorporeal circulation; immobilized enzymes; inborn metabolism disorder; photochemistry; plasmapheresis

Enzyme deficiencies associated with inborn metabolic defects are usually fatal within the first few years of life. Treatments such as diet manipulation, gene replacement therapy, chemotherapy, transfusions, transplantations, and peritoneal dialysis have produced marginal improvements in these patients. Enzyme replacement therapy is an appealing alternative or adjunct to these treatments. However, direct enzyme replacement has led to hypersensitivity responses in the hosts, and instability of such preparations has made use of such procedures impractical. We propose to explore immobilization chemistries for development of enzyme-activated surfaces for extracorporeal removal of toxic metabolites. We will use photochemical procedures to activate support matrices for subsequent coupling to the model enzyme, arginase. Successful demonstration of the improved enzyme activities afforded by this technology in an in vitro blood system will lead to continuation of this project with a consultant laboratory for Phase II animal model studies.

与先天代谢缺陷相关的酶缺乏是 通常在生命的最初几年内致命。治疗如 如饮食控制、基因替代疗法、化疗、 输血、移植和腹膜透析 对这些患者产生了微小的改善。 酶 替代疗法是一种有吸引力的替代疗法或辅助疗法 治疗。 然而，直接的酶替代导致 宿主的超敏反应以及此类反应的不稳定性 准备工作使得使用此类程序变得不切实际。 我们 建议探索固定化化学以开发 用于体外去除有毒物质的酶激活表面 代谢物。 我们将使用光化学程序来激活 用于随后与模型酶偶联的支持矩阵， 精氨酸酶。 改良酶的成功示范 该技术在体外血液系统中提供的活性 将导致该项目与顾问一起继续进行 II期动物模型研究实验室。