THERAPEUTIC URICASE FOR URIC ACID - INDUCED PATHOLOGIES

我们的长期目标是开发一种可用于治疗的尿酸酶 高尿酸血症和痛风的各种表现，包括痛风 关节炎(急性和慢性)组织和组织中的黄玉和尿酸盐沉积 器官和尿酸肾病。预计治疗性的 尿酸酶将能够完全清除体内的尿酸盐沉淀物。它 如果每隔一段时间少量服用，也能控制高尿酸血症。 治疗性尿酸酶应该能够溶解物质中的尿酸盐沉积 数小时或数天，并应立即缓解急性痛风 关节炎发作，没有复发的可能性。癌症患者 对巨大的肿瘤肿块进行侵袭性放疗或化疗 将受到保护，不会产生过多的尿酸盐。 该项目的具体目标是通过共价连接来修改 甲氧基聚乙二醇单甲氧基聚乙二醇是一种精选的高活性尿酸酶， 稳定性好，免疫原性可控。开发的步骤 均相的聚乙二醇尿酸酶进展顺利。动物毒理学研究将是 在小鼠、大鼠和狗身上完成，为提交 正在研究的新药编号和开始人类临床的许可 药代动力学和毒理学检测。

Our long-term goal is to develop a therapeutic uricase that can be used in hyperuricemia and the various manifestations of gout, including gouty arthritis (acute and chronic) tophi and urate deposits in tissues and organs, and uric acid nephropathy. It is expected that the therapeutic uricase will be able to remove completely urate deposits in the body. It will also control hyperuricemia if given at intervals in small amounts. Therapeutic uricase should be able to dissolve urate deposits in a matter of hours or days, and should provide immediate relief for acute gouty arthritis attacks, with no likelihood of recurrence. Cancer patients undergoing aggressive radiation or chemotherapy against large tumor masses will be protected from excessive urate production. The specific aims of this project are to modify by covalent attachment of monomethoxypolyethylene glycol (PEG) a selected uricase with high activity, good stability, and controlled immunogenicity. Procedures for developing a homogeneous PEG-uricase are well along. Animal toxicology studies will be done in mice, rats and dogs in preparation for submission for an Investigational New Drug Number and permission to begin human clinical testing for pharmacokinetics and toxicology.