THERAPEUTIC URICASE FOR URIC ACID - INDUCED PATHOLOGIES

治疗尿酸酶引起的尿酸病理

• 批准号: 3495585
• 负责人: ABRAHAM ABUCHOWSKI
• 金额: $ 4.29万
• 依托单位: ENZON, INC.
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-15 至 1987-02-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3495585
• 关键词: arthritis; drug adverse effect; drug metabolism; enzyme therapy; ethylene glycols; gout; hyperuricemia; inborn renal tubular transport disorder; neoplasm /cancer chemotherapy; nephrolithiasis; polyethylenes

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.

我们的长期目标是开发一种治疗性尿酸酶， 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）痛风石和尿酸盐沉积在组织中， 器官和尿酸肾病。 预期治疗剂 尿酸酶将能够完全去除体内的尿酸盐沉积物。 它 如果间隔给予少量，也将控制高尿酸血症。 治疗性尿酸酶应该能够溶解尿酸盐沉积物中的物质 几个小时或几天，并应提供立即缓解急性痛风 关节炎发作，不可能复发。 癌症患者 正在接受针对大肿瘤肿块的侵袭性放疗或化疗 将防止过量的尿酸盐产生。 该项目的具体目标是通过共价连接修饰 单甲氧基聚乙二醇（PEG）是一种选择性的高活性尿酸酶， 稳定性好，免疫原性可控。 制定一个 均一PEG-尿酸酶沿着。 动物毒理学研究将 在小鼠、大鼠和犬中进行，准备提交 试验用新药编号和开始人类临床试验的许可 药代动力学和毒理学测试