Commercialization Readiness Pilot for Flow Acceleration for Stroke Thrombolysis (FAST) System - Acute ischemic stroke (AIS) results from a blood clot in the neurovasculature and is the 5th leading cause of death and 1st leading cause of neurological disability in the United States (US). AIS impacts 700,000 Americans each year, with a 65% chance of death or severe disability. By 2030, the AIS economic burden will exceed $180B in the US alone. Standard of care AIS therapies include thrombolysis using alteplase (i.e., tissue plasminogen activator, tPA) within 4.5 hours of stroke onset and earliest possible thrombectomy for large vessel occlusions (out to 24hrs). In contrast to thrombectomy, thrombolysis does not require confirmation of a vessel occlusion. Because only ~10% of AIS victims are eligible for thrombectomy, thrombolysis remains a critical first line tool to treat those diagnosed with AIS. When employed, thrombolysis is associated with a ~15% improvement in stroke outcomes with ~10% fully recovering. However, due to the ~7% dose-dependent associated hemorrhage rate of alteplase, thrombolysis is contraindicated for mild and wake-up strokes which together make up ~60% of all AIS events. Due to safety concerns and limited reliability, usage of thrombolysis in the US remains low (~10%) with 90% of all AIS victims receiving only palliative care. There remains an urgent need to improve first line use of thrombolysis which can be expanded to all AIS victims. UN&UP has invented a novel adjunctive thrombolysis platform to safely accelerate alteplase to the obstructing blood clot, thereby overcoming the restrictive hemodynamics known to prevent alteplase from quickly reaching the occlusion. The proposed magnetic infusion platform overcomes this barrier by 1) adjunctively conveying alteplase to the clot’s surface more than 100X faster than normal biological diffusion (i.e., minutes vs. hours), and 2) mechanically mixing alteplase at the clot’s surface so that clots lyse faster. Because alteplase is not conjugated and the mode of action is purely mechanical in nature, FDA meetings support that a CDRH-led device pathway is appropriate in support of an IDE for an FDA Early Feasibility Study (EFS), which is a shorter and less expensive pathway compared to a traditional CDER-led IND process. Importantly, the technology is affordable, does not require precise focusing, and can be configured to travel with patients transferred for thrombectomy. Once proven safe and effective using current FDA approved alteplase labeling, UN&UP intends to expand thrombolysis to mild and wake up strokes by increasing the lysis efficacy of smaller alteplase doses known not to induce hemorrhage. If successful, thrombolysis could be safely extended to all AIS victims for the first time, which is 10X more than currently treated. To help commercialize this novel technology, this project’s aim is to evaluate safety and efficacy using an in vivo rat embolic middle cerebral arterial occlusion model at the Henry Ford Neuroscience Institute, which is increasingly being used in support of FDA approvals for early clinical studies related to AIS.
