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 i nclude 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.
Acute ischemic stroke is the fifth leading cause of death and the leading cause of neurological disability, with more than 700,000 Americans stricken each year. Because transfer times to thrombectomy-capable stroke centers, which are located near or in highly-populated urban centers, can take more than two hours for rural populations, neurological outcomes are disproportionately worse as compared to urban-concentrated populations. For this Phase I proposal, UN&UP (short for ?Unmet Needs and Underserved Populations?) will develop a magnetism-based mobile-health neuroprotection platform that overcomes the restrictive hemodynamics formed as a consequence of the occlusive clot so that neuroprotective agents are better delivered into the ischemic volume, therefore preserving and protecting the brain during long transfers for rural patients.