Acute ischemic stroke (AIS) is the leading cause of adult disability. Reperfusion therapies are the only FDA approved treatments for AIS but are limited because of narrow therapeutic time windows. We believe a highly promising approach to develop new stroke treatments is to initiate a neuroprotective agent early after stroke onset to reduce infarct progression before, or at the time of, reperfusion therapy. Our group has found that the IL-6 receptor blocker tocilizumab, (an FDA approved medication used for rheumatoid arthritis) is profoundly neuroprotective in reducing infarct volume and improving neurological outcome in rodent models of stroke in males and females and in aged animals. The primary objective of this proposal is to determine if tocilizumab can indeed slow infarct progression and extend the therapeutic window for reperfusion therapy using IV t-PA in a highly clinically relevant thromboembolic model and in a suture model that could be applied as a surrogate of the mechanical thrombectomy (MT) (Specific Aim 2). In order to design a clinical trial to test the efficacy of thrombectomy, we will then determine if tocilizumab can extend the therapeutic window of t-PA and MT in various clinically relevant models that simulate clinical risk factors for stroke incidence and severity. These models include advanced age, hypertension, diabetes, and will examine both sexes (Specific Aim 3). Assuming we will be asked to join the Stroke Preclinical Assessment Network (SPAN) to test tocilizumab as part of the consortium effort, we will begin initial communications with the other centers recruited to SPAN to establish optimal approaches to evaluate other candidate drugs (Specific Aim 3). We will certainly be willing to participate and use our many years of expertise in translational stroke research to evaluate other treatment candidates as part of the SPAN activities.

Public Health Relevance

Stroke is the number one cause of adult disability in the United States and with the aging population costs for stroke care over the next 50 years are projected to reach trillions of dollars. The overall goal of this project is to investigate the potential of the IL6 receptor blocker tocilizumab, an FDA approved medication used for rheumatoid arthritis, as a new treatment for stroke. Our lab has generated data demonstrating that tocilizumab is beneficial in reducing functional deficits and histological damage caused by stroke, and is efficacious in aged animals of both sexes. We will further evaluate this drug through the Stroke Preclinical Assessment Network (SPAN) mechanism and intend to utilize our local expertise in preclinical testing to help evaluate other candidate drugs selected for further testing through the SPAN.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZNS1)
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Bosetti, Francesca
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University of Texas Health Science Center Houston
Schools of Medicine
United States
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