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

急性缺血性中风(AIS)是由神经血管中的血块引起的。AIS是第五大致病原因 在美国(美国)死亡，是神经性残疾的主要原因。AIS将打击的不止是 2018年美国人将达到70万人，尽管中风护理最近取得了进展，但死亡的可能性仍为65% 或严重残疾。到2030年，预计仅在美国，AIS的经济负担就将超过1800亿美元。 标准护理AIS疗法包括在卒中发病4.5小时内进行溶栓治疗和 大血管闭塞应尽早行取栓治疗。然而，尽管血栓切除术被证明是 尽管如此，农村人口早期血栓摘除的机会很少，仍然导致护理方面存在很大差距。 在美国，血栓摘除手术主要在近170家综合中风中心之一进行 (CSCS)。由于与建立和维护CSC相关的成本相当高，这些中心是 集中在人口稠密的城市中心附近，可以提供更大的病人数量。然而， 结果是，超过一半的美国人面临着超过一个小时的转移时间，对于农村AIS来说 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。作为一名 结果，农村AIS患者的神经结局往往更差。而神经保护剂是 在长时间移植过程中，它们可能是保存大脑的强大工具，但它们尚未在临床上被证明有效 学习。这种差异的一个原因是闭塞的血液凝块导致血流动力学受限。 这会阻止神经保护剂有效地到达血栓附近和周围的缺血区。如果这个 如果克服了血流动力学限制，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，可以克服不良中风-- 相关的血流动力学，以便神经保护剂更好地输送到缺血区。这个 这项技术通过一种模式将氧化铁纳米颗粒输送到缺乏血液流动的缺血区域 对结合药物和非结合药物有效的作用。重要的是，该系统是负担得起的 被设计成在转移期间与AIS受害者一起旅行。而神经保护剂的结合有望 大幅提高效率，监管讨论支持该技术可以首先在 CDRH IF治疗药物是不结合的。该团队反映了磁学、机器人、纳米粒子、冲程和 神经保护专家，他们已经证明了以前的商业成功。第一阶段的工作重点是 平台的概念证明。目标包括1)原型工作站的构建，2)原型涂布 氧化铁颗粒制剂，3)CTA/MRA体外大血管闭塞模型疗效研究 卒中数据集，以及4)使用已知的AIS动物模型进行体内疗效和安全性评估。在.之前 第二阶段，计划召开一次FDA会议，告知监管途径。在第二阶段，最好的神经保护剂 将对药物进行鉴定和比较，并进行生物兼容性研究。

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.