Nitric oxide releasing nanomatrix to enhance dialysis fistula maturation

超过500，000名美国患者患有终末期肾病，超过80%的患者使用血液透析作为其治疗方法。 肾脏替代方式的选择。透析病人护理的致命弱点是发展一种 功能和持久的血管通路，优选动静脉瘘（AVF）。每年的治疗费用 血管通路功能障碍总计超过10亿美元。这主要是因为， 未成熟的AVF。创建后，60%的AVF未能成功成熟用于透析，原因是 早期静脉新生内膜发展和血管舒张不足。目前，没有有效的 促进血管通路成熟的治疗。 Endomimetics开发了一种释放一氧化氮（NO）的纳米基质凝胶， 天然内皮的特性。这种纳米基质可以在创建时应用于透析AVF上。在 我们的I期SBIR，纳米基质凝胶显示了30天内NO的释放，抑制了新生内膜的形成， 在大鼠AVF模型中，本发明的方法可以减少增生和炎性标志物的表达。内模 纳米基质凝胶是生物相容的肽基材料，并使炎症反应的风险最小化。 在这一II期SBIR中，我们建议评估纳米基质凝胶对AVF成熟的有效性， 临床相关时间点。目的1将包括评价凝胶化性质，离体血管扩张， 以及评价NO对抑制炎症的作用。在与李博士的合作下， 位于伯明翰的亚拉巴马，目的2和3将评估Endomimetics纳米基质凝胶在一个受试者中的功效。 建立啮齿类动物AVF模型，并在猪模型中。 促进AVF成熟的内模拟物NO释放纳米基质凝胶的开发可能具有 对需要透析的患者的治疗产生重大影响。随着第二阶段的顺利完成，我们 计划与FDA进行讨论。

More than 500,000 U.S. patients have end stage renal disease and over 80% utilize hemodialysis as their renal replacement modality of choice. The Achilles Heel in the care of dialysis patients is the development of a functioning and durable vascular access, preferably an arteriovenous fistula (AVF). The annual cost of treating vascular access dysfunction totals over one billion US dollars. This is largely due to the high proportion of AVFs that fail to mature. After creation, sixty percent of AVFs fail to mature successfully for dialysis use, due to early venous neointimal development and inadequate vasodilation. At present, there are no effective therapies to promote vascular access maturation. Endomimetics has developed a nitric oxide (NO) releasing nanomatrix gel that mimics the characteristic properties of native endothelium. This nanomatrix can be applied on the dialysis AVF at the time of creation. In our Phase I SBIR, the nanomatrix gel demonstrated release of NO over 30 days, inhibited neointimal hyperplasia, and reduced expression of inflammatory markers in a rat AVF model. The Endomimetics nanomatrix gel is a biocompatible peptide based material and minimizes the risk of inflammatory responses. In this Phase II SBIR, we propose to evaluate the efficacy of the nanomatrix gel for AVF maturation at a clinically relevant time point. Aim 1 will include evaluation of gelation properties, ex vivo blood vessel dilation, and assessment of NO effects on inhibition of inflammation. In collaboration with Dr. Lee at the University of Alabama at Birmingham, Aims 2 and 3 will evaluate the efficacy of the Endomimetics nanomatrix gel in an established rodent AVF model, and in a porcine model. Development of the Endomimetics NO releasing nanomatrix gel that promotes AVF maturation may have significant impact in the treatment of patients requiring dialysis. With successful completion of Phase II, we plan to move forward in discussion with the FDA.