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

描述（由申请人提供）：目前只有一种获批的治疗急性缺血性卒中的药物，即t-PA。t-PA是一种非常有益的治疗方法，但由于担心通常致命的副作用（称为出血性转化）而严重利用不足。临床上迫切需要一种诊断方法来识别出血性转化（HT）风险较高和较低的患者。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的分子诊断的实用性。在这项研究中，我们将确定最能预测结果的c-Fn阈值水平，确定c-Fn的升高是否具有时间依赖性，并在治疗期间跟踪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（MMP 9），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和增加使用t-PA/溶栓治疗中风。这项验证研究开发了第一个基于生物标志物的诊断，以帮助医生识别急性缺血性卒中的血栓破裂治疗导致的高风险和低风险出血患者。成功的开发将提高这种高度有益的治疗的安全性和使用率，并降低中风导致的整体医疗保健成本。

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.