Reuter-Rice Submits U54 Sub-Contract Application

Kudos to Karin Reuter-Rice, associate professor, and her entire team for the submission of her U54 sub-contract application with Wake Forest (SoM) entitled “Biologic Markers of Persistent Concussive Symptoms in Early and Middle Adolescents." This proposal requests funding for a five-year period with a start date of Oct. 1, 2019.

It is estimated that close to 1 million children (age 17 or younger) are treated in Emergency Departments annually for mild traumatic brain injury (mTBI). Adolescent mTBI is considered a silent epidemic because of staggering reports of increased incidence within this age group. While many adolescents quickly return to play and learn, there is a subset of adolescents that experience persistent concussive symptoms (PCS). PCS is defined as cognitive, functional, and/or behavioral (neurologic) symptoms that persist beyond 3-months after mTBI. PCS is associated with lost school days and activities because of sleep dysregulation, headaches, difficulty with memory or concentration and/or physical limitations. Therefore, early identification of those at risk for PCS would radically impact the timing, evaluation and effectiveness of treatment strategies for mTBI. However, prognostic protein and genetic biomarkers do not yet exist. Our group has preliminary evidence of novel genetic markers that may objectively reflect underlying risk for PCS in adolescent after mTBI. Our group has found biologic protein and genetic signals within the neuroinflammatory and immune gene-rich regions that may begin to explain PCS. In addition, our group found sex-based differences in injury response after mTBI. The goal of this project is to address the following aims. Aim 1: To acquire high-quality quantitative blood-based measures from an adolescent cohort (N=500) via cross-sequential study design enriched for acute (< 3 days) and persistent (> 3 months) concussive symptoms for the purposes of blood-based biometric discovery and validation, as well as large-scale data sharing via BioSEND. Aim 2: To use blood-based protein and genetic data acquired in SA1 to characterize the effects of concussive head impacts on brain structure and function among participants with acute/persistent concussive symptoms within the adolescent population using a linear mixed modeling approach. Aim 3: Discovery/Validation Phases: To identify the most sensitive and specific neuroinflammatory and immune related proteins and genetic markers acquired as part of SA1 for characterizing acute (< 3 days) and persistent (> 3 months) symptoms that result from concussive head impacts within the adolescent population using a data-driven predictive analytic approach. We will use rigorous and reproducible methods to triangulate protein and genetic biomarker data with common data elements and leverage the U54 multi-modal partner projects to deeply phenotype and risk stratify children for PCS. This project will expand our knowledge of known and novel neuroinflammatory and immune related protein and genetic biomarkers in mTBI. It will delve into whether sex and age-based difference are associated with PCS. Our findings will be validated so that we may translate these biologic signatures into risk algorithms. By identifying those adolescents most at risk for PCS after experiencing mTBI, we could begin to innovate personalized medicine treatments approaches to improve health outcomes.