Permanent Vasodilators for Improved Hemodialysis Access

永久性血管扩张剂可改善血液透析的可及性

• 批准号: 6833740
• 负责人: F Nicholas Franano
• 金额: $ 15.83万
• 依托单位: PROTARA THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6833740
• 关键词: Escherichia coli; drug design /synthesis /production; elastases; enzyme activity; hemodialysis; laboratory rabbit; microorganism culture; molecular cloning; nonhuman therapy evaluation; protein purification; protein quantitation /detection; recombinant DNA; vasodilation; vasodilators

DESCRIPTION (provided by applicant): The vast majority of patients with end-stage renal disease (ESRD) undergo periodic external blood filtering, a process known as hemodialysis. More than 300,000 patients in the United States currently depend on hemodialysis for their survival, and at least 90,000 new patients will begin hemodialysis this year. To treat ESRD by hemodialysis, vascular surgeons must create access sites in the body that allow the patient's blood to be passed through a hemodialysis machine. Unfortunately, almost 100% of the access sites will fail over time, usually due to inadequate vessel size and narrowing of the vein leading away from the site. Creating and maintaining these access sites is one of the most difficult and expensive components of ESRD treatment, and accounts for up to 50% of the total costs for each patient during the first year of hemodialysis. The annual domestic cost of hemodialysis access is estimated to be $1.5 billion, and is primarily paid through Medicare. Proteon Therapeutics has developed an innovative solution to this long-standing clinical problem. The company's first generation drug improves on current methods by permanently dilating the inflow artery and outflow vein at the time of access site creation, making the access site less susceptible to obstruction and failure. The objective of this Phase I research project is to develop a new, second generation drug candidate with improved pharmaceutical characteristics. To achieve this objective, the project will isolate and complete lab-scale synthesis of the new candidate drug. The candidate will then be purified and subjected to a series of in vitro biochemical assays to demonstrate that it retains its' intended activity. The new drug candidate will then be tested using in vivo models to demonstrate that it can deliver target levels of permanent blood vessel dilation in a clinically relevant model system. Successful completion of this SBIR Phase I research project will provide a rational basis for continuing the development of Proteon's technology into SBIR Phase II, where Proteon will seek to manufacture a cGMP-grade drug preparation, perform non-clinical toxicity and pharmacology studies, and complete a Phase I/II human clinical trial.

描述（由申请人提供）： 绝大多数患有终末期肾病（ESRD）的患者接受定期外部血液过滤，这一过程称为血液透析。美国目前有30多万患者依靠血液透析生存，今年将有至少9万名新患者开始血液透析。为了通过血液透析治疗终末期肾病，血管外科医生必须在体内建立通路部位，使患者的血液通过血液透析机。不幸的是，随着时间的推移，几乎100%的入路部位会失败，通常是由于血管尺寸不足和远离该部位的静脉变窄。创建和维护这些入路部位是ESRD治疗中最困难和最昂贵的组成部分之一，在血液透析的第一年中占每位患者总成本的50%。国内每年的血液透析费用估计为15亿美元，主要通过医疗保险支付。Proteon Therapeutics为这个长期存在的临床问题开发了一种创新的解决方案。该公司的第一代药物改进了目前的方法，在创建穿刺部位时永久扩张流入动脉和流出静脉，使穿刺部位不易阻塞和失败。该I期研究项目的目标是开发一种新的第二代候选药物，具有更好的药物特性。为了实现这一目标，该项目将分离并完成新候选药物的实验室规模合成。然后将候选物纯化并进行一系列体外生物化学测定，以证明其保留其预期活性。然后将使用体内模型对新药候选物进行测试，以证明它可以在临床相关模型系统中提供永久性血管扩张的目标水平。SBIR第一阶段研究项目的成功完成将为Proteon的技术继续发展到SBIR第二阶段提供合理的基础，Proteon将寻求制造cGMP级药物制剂，进行非临床毒性和药理学研究，并完成I/II期人体临床试验。