c-FN as a predictor of hemorrhagic transformation in t-PA treated stroke patients

描述（由申请人提供）：目前批准的治疗急性缺血性卒中的药物只有t-PA一种。t-PA是一种非常有益的治疗方法，但由于担心经常致命的副作用，即出血转化，因此严重未得到充分利用。有一个关键的临床需要诊断，以确定患者是在高和低风险的出血性转化（HT）。初步研究表明，血浆细胞纤维连接蛋白（c-Fn）水平可预测t-PA诱导的HT。我们将收集患者样本并进行验证研究，以确认c-Fn作为预测更严重形式HT的分子诊断的效用。在本研究中，我们将确定最能预测预后的c-Fn阈值水平，确定c-Fn升高是否与时间有关，并通过治疗跟踪c-Fn水平。此外，我们将分析其他血浆生物标志物，基质金属蛋白酶9 (MMP9)，载脂蛋白C-III （Apo-C）和血清淀粉样蛋白A （SAA）作为c-Fn的潜在贡献者，以更准确地预测HT。一个成功的诊断将大大提高安全性，并增加t-PA/溶栓药物在卒中治疗中的使用。这项验证性研究开发了第一个基于生物标志物的诊断，以帮助医生识别因急性缺血性中风的凝块破裂治疗而导致出血的高风险和低风险患者。成功的开发将提高这种非常有益的治疗方法的安全性和使用率，并降低中风导致的总体医疗保健成本。

DESCRIPTION (provided by applicant): Currently there is only one approved drug treatment for acute ischemic stroke, t-PA. t-PA is a highly beneficial treatment but is severely underutilized due largely to fear of an often fatal side effect called hemorrhagic transformation. There is a critical clinical need for a diagnostic to identify patients that are at high and low risk of hemorrhagic transformation (HT). A preliminary study showed that plasma level of cellular fibronectin (c-Fn) was predictive of t-PA induced HT. We will collect patient samples and perform a validation study to confirm the utility of c-Fn as a molecular diagnostic for the prediction of more severe forms of HT. In this study we will determine the threshold levels of c-Fn that are most predictive of outcome, determine if the elevation of c-Fn is time dependant, and follow c-Fn levels through treatment. In addition we will analyze additional plasma biomarkers, matrix metalloprotease 9 (MMP9), apolipoprotein C-III (Apo-C), and serum amyloid A (SAA) as potential contributors to c-Fn to more accurately predict HT. A successful diagnostic would greatly improve safety and increase use of t-PA/thrombolytics in the treatment of stroke. This validation study develops the first biomarker-based diagnostic to aid physicians in the identification of patients with high and low risk of bleeding as a result of clot busting treatment of acute ischemic stroke. Successful development will increase safety and usage of this highly beneficial treatment as well as lower overall healthcare cost as a result of stroke.