Development of Stroke Point of Care Immunoassay for Cellular Fibronectin

描述（由申请人提供）：中风是美国残疾的主要原因和第三大死亡原因，估计2006年对经济造成的间接和直接损失达600亿美元。中风的即时治疗对于保护脑组织和最终恢复至关重要。对于缺血性卒中，其约占所有卒中的五分之四，已证明通过组织纤溶酶原激活剂（tPA）的溶栓治疗在症状发作的关键前3小时内有效。不幸的是，研究表明，6-11%接受静脉tPA治疗的患者发生症状性出血。对这种严重且通常致命的副作用的恐惧阻止了这种疗法在缺血性卒中人群中的广泛使用和充分获益。 该SBIR II期申请提出开发蛋白质组学标志物细胞纤连蛋白（c-Fn）的即时快速诊断检测，3项独立研究表明，c-Fn可预测tPA治疗患者的出血性转化，灵敏度为100%，可辅助治疗决策。该提案的目标是创建一种基于侧向流技术的c-Fn快速检测方法，能够在10分钟内获得结果，实现<10%的检测间和检测内变异性，并实现低于25美元的总生产成本。 公共卫生相关性： 项目叙述医生必须在关键的3小时时间窗内决定使用凝块破坏剂tPA治疗缺血性卒中患者。入院时患者血液中细胞纤连蛋白（c-Fn）的量可以确定患者是否处于后续出血的高风险或低风险，担心这会阻止tPA的广泛使用。该提案开发了一种在10分钟内完成的快速c-Fn测试，以帮助急性缺血性卒中患者的治疗决策，从而提高患者的安全性，减少卒中的长期残疾，并降低长期医疗保健支出。

DESCRIPTION (provided by applicant): Stroke is the leading cause of disability and the third leading cause of death in the U.S., with an estimated $60 billion negative impact upon the economy in indirect and direct costs in 2006. Immediate treatment of stroke is critical for preservation brain tissue and ultimate recovery. For ischemic stroke, which comprises approximately four-fifths of all strokes, thrombolytic therapy by tissue plasminogen activator (tPA) has been proven to be effective in the critical first 3 hours from symptom onset. Unfortunately, studies have shown symptomatic hemorrhagic occurs in 6-11% of patients treated with intravenous tPA. Fear of this severe and often deadly side effect prevents the widespread use and full benefit of this therapy in the ischemic stroke population. This SBIR Phase II application proposes the development of a point-of-care rapid diagnostic test for the proteomic marker cellular fibronectin (c-Fn), which has been shown in 3 independent studies to predict hemorrhagic transformation in tPA-treated patients with a sensitivity of 100%, as an aid to treatment decision. The goal under this proposal is to create a rapid test for c-Fn based on lateral flow technology with the ability to obtain a result within 10 minutes, achieve inter- and intra-assay variability of <10%, and achieve a total production cost of under $25. PUBLIC HEALTH RELEVANCE: Project Narrative Physicians must decide on treatment of an ischemic stroke patient with a clot buster, tPA, within a critical 3 hour time window. The amount of cellular fibronectin (c-Fn) in the blood of patients at admission can identify if the patient is at high or low risk for a subsequent hemorrhage, fear of which prevents widespread useage of tPA. This proposal develops a rapid c-Fn test completed in 10 minutes to aid in the treatment decision of acute ischemic stroke patients that would lead to increase in patient safety, decrease in the long-term disability of stroke, and lower long-term healthcare spending.