Permanent Vasodilators for Improved Hemodialysis Access

描述(由申请人提供)： 绝大多数终末期肾病(ESRD)患者都会定期进行体外血液过滤，这一过程被称为血液透析。美国目前有30多万名患者依靠血液透析生存，今年将至少有9万名新患者开始血液透析。要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道，允许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%的接入站点将失败，通常是由于血管大小不足和从站点引出的静脉变窄。创建和维护这些访问站点是ESRD治疗中最困难和最昂贵的部分之一，在血液透析的第一年，每个患者的总成本高达50%。美国国内每年的血液透析费用估计为15亿美元，主要通过联邦医疗保险支付。蛋白质治疗公司已经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在现有方法的基础上进行了改进，在创建访问站点时永久扩张流入动脉和流出静脉，使访问站点不太容易受到阻塞和故障的影响。这一第一阶段研究项目的目标是开发一种新的、具有改进的药学特性的第二代候选药物。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，该候选者将被提纯，并接受一系列体外生化分析，以证明其保持其预期的活性。然后，这种新的候选药物将通过体内模型进行测试，以证明它可以在临床相关的模型系统中提供永久血管扩张的目标水平。这一SBIR第一阶段研究项目的成功完成将为将Proteon的技术继续开发到SBIR第二阶段提供合理的基础，在第二阶段，Proteon将寻求生产cGMP级药物制剂，进行非临床毒性和药理学研究，并完成第一/第二阶段的人体临床试验。

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.