ENZYME IMMOBILIZATION FOR REMOVAL OF TOXIC METABOLITES

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。治疗方法如 比如饮食控制，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乎其微的改善。酶 替代疗法是一种吸引人的替代疗法或附加疗法。 治疗。然而，直接的酶替代已经导致 寄主的超敏反应及其不稳定性 准备工作使这种程序的使用不切实际。我们 建议探索固定化化学的发展方向 用于体外排毒的酶激活表面 代谢物。我们将使用光化学程序来激活 用于随后偶联到模型酶的载体基质， 精氨酸酶。改良酶的成功演示 这项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 第二阶段动物模型研究实验室。

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.