Stroke Preclinical Assessment Network (SPAN) – Tacilizumab for treatment of acute ischemic stroke

卒中临床前评估网络 (SPAN) – 他珠单抗治疗急性缺血性卒中

基本信息

项目摘要

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.
急性缺血性卒中(AIS)是成人残疾的主要原因。再灌注疗法是FDA唯一批准的AIS治疗方法,但由于治疗时间窗狭窄而受到限制。我们认为,开发新的卒中治疗方法的一个非常有前途的方法是在卒中发作后早期启动神经保护剂,以减少再灌注治疗前或再灌注治疗时的梗死进展。我们的研究小组发现,IL-6受体阻断剂托珠单抗(一种FDA批准的用于类风湿性关节炎的药物)在减少雄性和雌性以及老年动物中风啮齿动物模型中的梗死体积和改善神经学结果方面具有深刻的神经保护作用。该提案的主要目的是确定托珠单抗是否确实可以减缓梗死进展,并在高度临床相关的血栓栓塞模型和可用作机械血栓切除术(MT)替代品的缝合模型中使用IV t-PA延长再灌注治疗的治疗窗(具体目标2)。为了设计一项临床试验来测试血栓切除术的疗效,我们将确定托珠单抗是否可以在各种临床相关模型中延长t-PA和MT的治疗窗,这些模型模拟了卒中发生率和严重程度的临床风险因素。这些模型包括高龄、高血压、糖尿病,并将对两性进行检查(具体目标3)。假设我们将被要求加入卒中临床前评估网络(SPAN),以测试托珠单抗,作为联盟工作的一部分,我们将开始与招募到SPAN的其他中心进行初步沟通,以建立评估其他候选药物的最佳方法(具体目标3)。作为SPAN活动的一部分,我们当然愿意参与并利用我们在转化性卒中研究方面的多年专业知识来评估其他候选治疗方案。

项目成果

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Jaroslaw Aronowski其他文献

Jaroslaw Aronowski的其他文献

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{{ truncateString('Jaroslaw Aronowski', 18)}}的其他基金

Aryl hydrocarbon receptor and bilirubin as therapeutic target for ICH
芳烃受体和胆红素作为脑出血的治疗靶点
  • 批准号:
    10615880
  • 财政年份:
    2021
  • 资助金额:
    $ 50.69万
  • 项目类别:
Aryl hydrocarbon receptor and bilirubin as therapeutic target for ICH
芳烃受体和胆红素作为脑出血的治疗靶点
  • 批准号:
    10299427
  • 财政年份:
    2021
  • 资助金额:
    $ 50.69万
  • 项目类别:
Aryl hydrocarbon receptor and bilirubin as therapeutic target for ICH
芳烃受体和胆红素作为脑出血的治疗靶点
  • 批准号:
    10408850
  • 财政年份:
    2021
  • 资助金额:
    $ 50.69万
  • 项目类别:
Humanin and Intracerebral Hemorrhage
护脑素与脑出血
  • 批准号:
    10316990
  • 财政年份:
    2019
  • 资助金额:
    $ 50.69万
  • 项目类别:
Humanin and Intracerebral Hemorrhage
护脑素与脑出血
  • 批准号:
    10547749
  • 财政年份:
    2019
  • 资助金额:
    $ 50.69万
  • 项目类别:
Neutrophils in Recovery after ICH
ICH后中性粒细胞的恢复
  • 批准号:
    9816107
  • 财政年份:
    2016
  • 资助金额:
    $ 50.69万
  • 项目类别:
Optimized lactoferrin for treatment of intracerebral hemorrhage
优化乳铁蛋白治疗脑出血
  • 批准号:
    9016473
  • 财政年份:
    2015
  • 资助金额:
    $ 50.69万
  • 项目类别:
Optimized lactoferrin for treatment of intracerebral hemorrhage
优化乳铁蛋白治疗脑出血
  • 批准号:
    9248446
  • 财政年份:
    2014
  • 资助金额:
    $ 50.69万
  • 项目类别:
Optimized lactoferrin for treatment of intracerebral hemorrhage
优化乳铁蛋白治疗脑出血
  • 批准号:
    8831091
  • 财政年份:
    2014
  • 资助金额:
    $ 50.69万
  • 项目类别:
Treatment of secondary injury after ischemic stroke through targeting microglia
通过靶向小胶质细胞治疗缺血性中风后继发性损伤
  • 批准号:
    8573537
  • 财政年份:
    2013
  • 资助金额:
    $ 50.69万
  • 项目类别:

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