Diagnostic protein biomarkers for severe, moderate and mild traumatic brain injury

Traumatic Brain Injury (TBI) is a major problem in military and civilian medicine. Yet, there are no simple non-invasive diagnostics for TBI. Our goal is to develop and clinically validate blood-based biomarker assays for the diagnosis, prognosis and management of mild, moderate and severe TBI patients. These assays will ultimately be suitable for deployment to far-forward combat environments. Using a proteomic and systems biology approach, we identified over 20 candidate biomarkers for TBI and developed robust ELISAs for at least 6 candidate biomarkers, including Ubiquitin C-terminal hydrolase- L1 (UCH-L1), Glial Fibrillary Acidic Protein (GFAP) and a 145 kDa breakdown products of αII-spectrin (SBDP 145) generated by calpain proteolysis. In a multi-center feasibility study (Biomarker Assessment For Neurotrauma Diagnosis And Improved Triage System (BANDITS), we analyzed CSF and blood samples from 101 adult patients with severe TBI [Glasgow Coma Scale (GCS) ≤ 8] at 6 sites and analyzed 27 mild TBI patients and 5 moderate TBI patients [GCS 9-15] from 2 sites in a pilot study. We identified that serum levels of UCH-L1, GFAP and SBDP145 have strong diagnostic and prognostic properties for severe TBI over controls. Similarly initial post-TBI serum levels (< 6 h) of UCH-L1 and GFAP have diagnostic characteristics for moderate and mild TBI. We are now furthering assay production, refining assay platforms (both benchtop and point-ofcare/ handheld) and planning a pivotal clinical study to seek FDA approval of these TBI diagnostic assays.