Combination treatment with Vepoloxamer and tPA for acute stroke

摘要 中风是世界范围内导致死亡和残疾的主要原因之一，主要影响老年人。组织纤溶酶原 激活剂(TPA)是美国食品和药物管理局(FDA)批准的唯一一种治疗方法，其使用范围仅限于8.5% 中风患者。因此，迫切需要开发新的和更广泛的实用疗法来治疗急性胰腺炎 缺血性中风。维泊洛沙姆是一种专有的两亲性共聚物，具有流变性。 特性，目前正在进行针对镰状细胞患者的全球III期临床试验 疾病。我们的初步研究表明，维泊洛沙姆联合tPA 4h给药 栓塞性卒中后促进再通和溶栓可减少缺血性神经元损伤和 改善幼年成年大鼠的神经预后，但不增加脑出血。我们还发现 血小板源外切体在维泊洛沙姆治疗增生性心脏病中的作用 TPA-溶栓治疗。在此应用中，我们建议研究维泊洛沙姆与tPA联合应用的效果。 急性卒中与联合溶栓治疗的分子机制探讨 老年雄性和雌性大鼠的神经血管功能。从该应用程序生成的数据可以提供 急性卒中患者的新的和潜在有用的治疗策略。

Abstract Stroke is one of leading causes of death and disability worldwide, mainly affecting elderly. Tissue plasminogen activator (tPA), the only Food and Drug Administration (FDA) approved treatment, is limited in its use to < 8.5% of stroke patients. Therefore, there is a compelling need to develop new and broader utility therapies for acute ischemic stroke. Vepoloxamer is a well characterized proprietary amphipathic copolymer with rheological properties, which is currently under investigation in a global phase III clinical trial for patients with sickle cell disease. Our preliminary studies demonstrate that administration of Vepoloxamer in combination with tPA 4h after embolic stroke facilitates recanalization and thrombolysis reduces ischemic neuronal damage and improves neurological outcome, but does not increase cerebral hemorrhage in young adult rats. We also found that platelet-derived exosomes contribute to the therapeutic effect of Vepoloxamer on enhanced tPA-thrombolysis. In this application, we propose to investigate effect of Vepoloxamer in combination with tPA on acute stroke and molecular mechanisms underlying the combination therapy on the thrombolysis and neurovascular function in the aged male and female rats. Data generated from this application may provide a novel and potentially useful treatment strategy for patients with acute stroke.