A novel therapeutic antibody for treatment of ischemic stroke.

描述（由申请人提供）：中风是美国第三大死亡原因。尽管其流行，目前的治疗选择是有限的，存活的中风仍然与严重的发病率问题。用于缺血性中风的最新疗法阿替普酶在十多年前被FDA批准，并且由于如果在急性事件后超过3小时施用则可能诱发出血并发症而具有严重的局限性，并且其使用被禁忌用于出血性中风。即便如此，临床研究表明，这种药物与随后的抗血栓治疗（如阿司匹林）联合使用可改善患者的预后。然而，这些药物不能与tPA同时使用，因为它们可能加剧出血，尽管已知血小板在由初始缺血事件触发的下游事件中起作用。本申请中描述的方法是开发针对中风的新靶标的治疗性抗体。不仅血小板GPIba相互作用提供了一个有前途的目标，以开发抗血栓药物，降低出血并发症的可能性，但这种相互作用似乎也发挥了重要作用，在再灌注损伤过程中与炎症内皮反应相关的继发性血栓形成。该I期项目中描述的研究的成功结果，加上II期计划的研究，将使我们能够开发概念证明并完成毒理学研究，用于治疗缺血性卒中的有前途的新治疗药物。公共卫生关系：中风是美国第三大死亡原因。尽管其流行，目前的治疗选择是有限的，存活的中风仍然与严重的发病率问题。最近批准的缺血性卒中治疗（药物）Acteplase是FDA在十多年前批准的，并且具有严重的局限性，因为如果在卒中发生后超过3小时给药，其可能诱导出血并发症，这极大地限制了其使用。如果成功的话，我们提出的研究可能会导致一种更有效地治疗缺血性中风的新药。

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.