NOVEL ENZYME FORMULATION FOR TREATMENT OF HYPEROXALURIA

用于治疗高草酸尿症的新型酶制剂

• 批准号: 6404537
• 负责人: Saraswathi Mandapati
• 金额: $ 8.67万
• 依托单位: ALTUS PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6404537
• 关键词: biotechnology; carbon carbon lyase; crosslink; crystallization; drug delivery systems; drug design /synthesis /production; oral administration; oxalates; oxidoreductase; primary hyperoxalurias; proteolysis

DESCRIPTION (provided by applicant): Design of new efficient drug delivery systems for proteins is one of the major themes of modern biotechnology and biopharmaceutical industry. We found that crosslinked enzyme crystals (CLECs) show stability under low pH, on storage and against proteolysis. These properties make them ideal for gut lumenal therapy. The patient would swallow a tablet or liquid suspension of CLEC particles composed of a needed metabolic enzyme or protein. The CLEC agent would survive the harsh acidic pH and proteolytic environment of the stomach, and pass into the proximal small intestine. The CLEC particle would then carry out its therapeutic biochemistry within the gut lumen while remaining resistant to degradation by endogenous proteases. In this Phase I study, we propose to develop two types of CLECs: Oxalyl-CoA decarboxylase for oral lumenal therapy and Oxalate oxidase to be used in the extracorporeal device/dialysis equipment. The Oxalyl-CoA decarboxylase-CLEC will perform its action in the duodenum while remaining as crystalline material or by release of activity by dissolution of the CLEC particle. This target was chosen to address the problems of current therapies of hyperoxaluna caused by excessive absorption of oxalate due to the absence of Oxalobacter formigenes bacterium in the intestine or due to inflammatory bowel disease. In addition, Oxalate oxidase-CLEC may be used in dialysis equipment or extracorprealdevices to reduce the oxalate content of blood in patients with Primary Hyperoxaluria. If successful, these approaches will lead to the introduction of novel, efficient enzyme therapy for the prevention of Oxalate Kidney Stones. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE

描述（申请人提供）：新型高效给药系统的设计 蛋白质系统是现代生物技术的主要主题之一， 生物制药行业。我们发现交联酶晶体（CLECs） 在低pH、储存和抗蛋白水解下显示稳定性。这些 这些特性使它们成为肠腔内治疗的理想选择。病人会吞下一个 CLEC颗粒的片剂或液体悬浮液，所述CLEC颗粒由所需的代谢物质组成， 酶或蛋白质。CLEC试剂将在苛刻的酸性pH下存活， 胃的蛋白水解环境，并进入近端小 肠子然后CLEC粒子将进行其治疗性的生物化学反应， 同时保持对内源性降解的抗性 蛋白酶在第一阶段研究中，我们建议发展两类社区学习中心： 用于口腔治疗的草酰辅酶A脱羧酶和草酸氧化酶 用于体外装置/透析设备。乙二酰辅酶A 脱羧酶-CLEC将在十二指肠中发挥作用， 晶体物质或通过溶解CLEC释放活性 粒子选择该靶点是为了解决当前治疗方法的问题 由于缺乏草酸盐而引起的草酸盐过度吸收引起的高尿酸血症 产草酸杆菌在肠道或由于炎症肠 疾病此外，草酸氧化酶-CLEC可用于透析设备或透析装置中。 体外装置，以减少患者血液中的草酸盐含量 原发性高尿酸血症。如果成功，这些方法将导致 引入新型、有效的酶疗法来预防草酸盐 肾结石 拟议商业应用：不可用