Consistent with the vision of the Analytical Validation of a Candidate Biomarker for Neurological Disease PAR, we assembled a multidisciplinary team and propose to conduct analytical validation of two emerging TBI biomarkers: Tau and phospho-Tau (P-Tau). Although recently FDA approved a pair of markers (neuronal cell body marker UCH-L1 and astroglia injury marker GFAP) to diagnose cranial CT abnormality in mild TBI patients, however, to date, there are no qualified and validated biomarkers linked directly to axonal degenerative axonal injury and after TBI, especially in the acute and subacute phases after TBU. Emerging literature evidence and our own data point to blood-based Tau/P-Tau levels can fill these unmet biomarker needs. We propose two types of context of use (COU) for Tau/ P-Tau as prognostic biomarkers for complicated mild TBI patients at risk for persistent post-concussive symptoms lasting more than 3 months. While Tau/ P- Tau are promising TBI prognostic biomarkers, there are significant knowledge gaps regarding Tau/P-Tau biomarkers, as well as their detection assays. In this proposed study, we will (1) create Tau and P-Tau gold standards and pooled positive/negative controls samples for use in Tau/P-Tau platform testing and standardization, (2) assess the analytical performance of new assay platforms for Tau/P-Tau at two analytical sites, (3) establish the baseline blood levels of Tau and P-Tau in normative controls of different adult age intervals, (4) provide supportive data for acute/subacute Tau and P-Tau levels as blood-based biomarker for the indicated COU, (5) establish the temporal profile of blood Tau, P-Tau levels in TBI patients of varying severity and injury types, and lastly (6) assemble Tau/P-Tau TBI biomarker qualification plan for submission to FDA's Biomarker Qualification Program.
To date, there is a lack of blood-based traumatic brain injury biomarkers that are linked directly to axonal injury and neurodegeneration after TBI. Based on collective literature and our own data, Tau protein and phospho-Tau (P-Tau) can provide following context of use: as prognostic biomarkers for complicated mild TBI patients at risk for persistent post-concussive symptoms lasting more than 3 months. The main objective of this proposal is to conduct analytic validation of Tau and P-Tau (at Thr-231) biomarkers on two advance assay platforms (Quanterix SIOMA, SOFIA-RCA). We obtained new preliminary data showing that both platforms have demonstrated assay sensitivity of measuring Tau and P-Tau in human serum and plasma samples.
