| Abstrakt: |
Introduction:Stroke is the 5th leading cause of death, and a leading cause of long-term disability in the US. Thus, there is a need for a rapid biomarker-based screen that enables an objective and timely diagnosis and better patient outcome; however, the lack of such a technology delays diagnosis and treatment, increases misdiagnosis, and leads to the overuse of thrombolysis in patients with stroke mimics.Methods:Here we present pilot data of a nanobiotechnology based test platform, in which enzyme-functionalized nanoparticles (TET, Tethered Enzyme Technology) are used for ultra-rapid biomarker detection. As proof of concept, we used TET to quantify the enzymatic activity of a widely studied brain injury biomarker, neuron-specific enolase (NSE), in a trial performed at a regional stroke center.Results:Plasma from 36 suspected stroke and 17 asymptomatic subjects (Total N=53) was tested to determine levels of the novel biomarker NSE catalytic activity (NSE-A) versus the conventional NSE protein (NSE-P). Based on clinical diagnoses, our data demonstrate a significant increase in the levels of NSE-A in subjects suffering from injury to neurons (BI, Brain Injury) compared to those with negative diagnoses (Neg, stroke mimics). Moreover, we show that NSE-A provides a considerable diagnostic advantage over the NIH Stroke Scale or NSE-P (Figure 1A-C) in both clinical utility and speed. In diagnosis of stroke mimics (including TIAs and Neg) versus BI, NSE-A showed significantly better performance than NIHSS or NSE-P, as shown by ROC and AUC analyses (Figure 1D).Conclusions:TET-based detection of NSE-A can rapidly differentiate patients suffering a neuronal injury, including stroke, from those presenting with stroke mimics. Upon further development of a point-of-care test for NSE-A and other biomarkers, TET could be an asset to ongoing efforts to streamline stroke patient care, reduce door to needle time, and decrease overall brain injury and long-term disability. |
