A novel therapeutic antibody for treatment of ischemic stroke.

描述(申请人提供)：中风是美国第三大死因。尽管中风很普遍，但目前的治疗选择有限，存活的中风仍然与严重的发病率问题有关。最新的治疗缺血性中风的药物Alteplase在十多年前被FDA批准，由于在急性事件发生后3小时以上使用可能会导致出血并发症，因此具有严重的局限性，对于出血性中风使用Alteplase是相反的。尽管如此，临床研究表明，将这种药物与随后的抗血栓治疗(如阿司匹林)相结合，可以改善患者的预后。然而，这些药物不能与tPA同时使用，因为它们有可能加剧出血，尽管已知血小板在最初的缺血事件引发的下游事件中发挥了作用。本申请中描述的方法是开发一种针对中风新靶点的治疗性抗体。血小板-GPIba的相互作用不仅为开发抗血栓药物提供了一个有希望的靶点，减少了出血并发症的可能性，而且这种相互作用似乎在再灌注损伤中与炎性内皮反应相关的继发性血栓形成中也发挥了重要作用。这个第一阶段项目中描述的研究的成功结果，加上第二阶段计划的研究，将使我们能够为治疗缺血性中风的一种有前途的新治疗剂开发概念证明和完成毒理学研究。公共卫生相关性：中风是美国第三大死亡原因。尽管中风很普遍，但目前的治疗选择有限，存活的中风仍然与严重的发病率问题有关。最近批准的治疗缺血性中风的药物Acteplase在十多年前得到了FDA的批准，但由于其在中风发生后3小时以上使用可能会导致出血并发症，因此具有严重的局限性，这极大地限制了其使用。如果成功，我们正在提议的研究可能会导致一种新的药物来更有效地治疗缺血性中风。

DESCRIPTION (provided by applicant): Stroke is the third leading cause of death in the United States. Despite its prevalence, current treatment options are limited and surviving stroke is still associated with serious morbidity issues. The most recent therapy for ischemic stroke, Alteplase, was approved by the FDA over a decade ago and has serious limitations due to the potential for inducing bleeding complications if administered more than 3 hours after the acute event, and its use is counter-indicated for hemorrhagic strokes. Even so, clinical studies suggest that the combination of this drug with subsequent anti-thrombotic treatment such as aspirin, improves patient outcome. However, such agents can not be used concurrently with tPA because of their potential to exacerbate bleeding despite the known role platelets play in the downstream events triggered by the initial ischemic event. The approach described in this application is to develop a therapeutic antibody directed against a novel target for stroke. Not only does the -platelet GPIba interaction provide a promising target to develop anti-thrombotics with a reduced potential for bleeding complications, but this interaction also appears to play a major role in the secondary thrombosis associated with inflammatory endothelial responses during reperfusion injury. A successful outcome of the research described in this Phase I project, coupled with the research planned for Phase II, would allow us to develop proof of concept and completion of toxicology studies for a promising new therapeutic agent for the treatment of ischemic stroke. PUBLIC HEALTH RELAVANCE: Stroke is the third leading cause of death in the United States. Despite its prevalence, current treatment options are limited and surviving stroke is still associated with serious morbidity issues. The most recently approved therapy (drug) for ischemic stroke, Acteplase, was approved by the FDA over a decade ago and has serious limitations because of its potential for inducing bleeding complications if administered more than 3 hours after the stroke has occurred, which greatly limits its use. If successful, the research we are proposing could lead to a new drug to more effectively treat ischemic stroke.