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

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.