Acute Ischemic Stroke Neuroprotection Platform to overcome Care Disparities for Rural Populations

急性缺血性卒中（AIS）是由神经血管中的血块引起的。AIS是第五大原因， 在美国（US），它是导致神经系统残疾的主要原因。AIS将打击超过 2018年有70万美国人，尽管最近中风护理取得了进展，但死亡率仍有65% 或严重残疾。到2030年，预计仅在美国，AIS的经济负担将超过1800亿美元。 AIS标准治疗包括在卒中发作后4.5小时内使用溶栓， 尽早对大血管闭塞进行血栓切除术。然而，尽管血栓切除术被证明 然而，农村人口早期血栓切除术的机会少，仍然导致护理方面的巨大差距。 在美国，血栓切除术主要在近170个综合卒中中心中的一个进行 （CSC）。由于建立和维护CSC的成本相当高，因此这些中心 集中在人口密集的城市中心附近，可以提供更大的患者量。但 结果是，超过一半的美国人面临超过一个小时的转移时间， 受害者占美国人口的近四分之一，转移延迟可能超过两个小时。作为 因此，农村AIS受害者的神经系统结果往往更糟。虽然神经保护剂是一种 在长期转移过程中保存大脑的潜在强大工具，它们尚未在临床上被证明有效 问题研究这种差异的一个原因是闭塞性血凝块导致血液动力学受限 其阻止神经保护剂有效地到达凝块附近和周围的缺血区域。如果这 如果血液动力学限制得到克服，农村人口将受益匪浅。 UN&UP发明了一种新型的基于纳米颗粒的移动健康平台，可以克服不利的中风， 相关的血流动力学，使得神经保护剂更好地递送到缺血体积。的 该技术使用以下模式将氧化铁纳米颗粒输送到缺血的血流剥夺区域： 对结合和非结合药物有效的作用。重要的是，该系统价格实惠， 在转移过程中与AIS受害者同行虽然神经保护剂的结合承诺， 实质性地提高效率，监管讨论支持该技术可以首先根据 如果治疗剂未缀合，则为CDRH。该团队反映了磁学，机器人，纳米粒子，中风， 神经保护专家，他们已经证明了先前的商业成功。第一阶段的工作重点是 平台的概念验证。目标包括1）原型工作站建设，2）原型涂层 氧化铁颗粒制剂，3）使用CTA/MRA的体外大血管闭塞体模有效性研究 中风数据集，和4）使用已知AIS动物模型的体内疗效和安全性评估。之前 第二阶段，计划召开一次FDA会议，通报监管途径。在第二阶段，最好的神经保护剂 将对试剂进行鉴定和比较，并进行生物相容性研究。

Acute ischemic stroke (AIS) results from a blood clot in the neurovasculature. AIS is the 5th leading cause of death in the United States (US) and is the leading cause of neurological disability. AIS will strike more than 700,000 Americans in 2018 and, despite recent advances in stroke care, there remains a 65% chance of death or severe disability. By 2030, it is expected that the AIS economic burden will exceed $180B in the US alone. Standard-of-care AIS therapies include the use of thrombolysis within 4.5 hours of stroke onset and thrombectomy for large vessel occlusions as early as possible. However, despite thrombectomy’s proven value, poor access to early thrombectomy for rural populations still results in large disparities in care. In the US, thrombectomies are largely performed at one of nearly 170 Comprehensive Stroke Centers (CSCs). Because considerable costs are associated with setting up and maintaining a CSC, these centers are concentrated near highly-populated urban centers, which can provide larger patient volumes. However, the consequence is that more than half of Americans face transfer times longer than an hour, and for rural AIS victims, who represent nearly a quarter of the US population, transfer delays can exceed two hours. As a result, neurological outcomes for rural AIS victims tend to be worse. While neuroprotective agents are a potentially powerful tool in preserving brain during long transfers, they have yet to be proven effective in clinical studies. One reason for this discrepancy is that the occlusive blood clot results in restrictive hemodynamics which prevent neuroprotectants from effectively reaching the ischemic region near and around the clot. If this hemodynamic limitation were overcome, the benefit to rural populations would be profound. UN&UP has invented a novel nanoparticle-based mobile-health platform which overcomes adverse stroke- associated hemodynamics so that neuroprotective agents are better delivered to the ischemic volume. The technology conveys iron oxide nanoparticles into the blood flow-deprived region of ischemia using a mode of action that is efficacious for conjugated and unconjugated drugs. Importantly, the system is affordable and designed to travel with the AIS victim during transfer. While conjugation of the neuroprotectant promises to substantially improve efficacy, regulatory discussions support that the technology could be first regulated under the CDRH if therapeutics are unconjugated. The team reflects magnetics, robotics, nanoparticle, stroke, and neuroprotection experts, who have demonstrated prior commercial successes. The Phase I effort focuses on proof of concept of the platform. The aims include 1) prototype workstation construction, 2) prototype coated iron oxide particle formulation, 3) in vitro large-vessel occlusion phantom efficacy studies using CTA/MRA stroke datasets, and 4) in vivo efficacy and safety assessments using a known AIS animal model. Prior to Phase II, an FDA meeting is planned to inform the regulatory pathway. In Phase II, the best neuroprotectant agents will be identified and compared, and biocompatibility studies will be conducted.