Saliva biomarkers for noninvasive diagnostics of acute mTBI in children

PROJECT SUMMARY Saliva biomarkers for noninvasive diagnostics of acute mTBI in children Pediatric mild TBI (mTBI) is a global health concern. However, there is no standard approach to diagnose pediatric mTBI. There is unmet need for standard, objective diagnostics of mTBI, a key element for making decisions about returning to learning and play, and preventing second impact syndrome. The ultimate goal of this SBIR project is to develop a rapid commercial test for noninvasive diagnostics of mTBI in children. The proposed Phase I research will provide proof-of-concept for the core technology: saliva biomarkers with high diagnostic accuracy and specificity for acute pediatric mTBI. Preliminary Studies (N=135 human subjects, 180 saliva samples) identified N=10 candidate saliva mTBI biomarkers in adults and showed potential to translate the technology for children. The candidate biomarkers were not confounded by time after injury, mTBI mechanism, CT scan finding, LOC duration, sex and age in healthy controls. SA1 will collect N=420 serial saliva samples from N=180 children age 8-17. mTBI patients (N=60, GCS=13-15) will be enrolled in Houston (40 ED patients, age 8-17) and San Diego (20 HS contact sport athletes, age 15- 17). Saliva and clinical outcome measures will be collected from mTBI and OI at T1-T3: ≤ 24h, 7d and 30d after injury, and at enrollment from healthy controls. Primary clinical endpoint: acute mTBI. Secondary clinical endpoint: persistent postconcussion symptoms (PPCS) at 30d, and prolonged Return To Play (RTP) ≥30d after mTBI. Controls (N=120): mild traumatic orthopedic injury without head injury (OI, ED patients and contact sport athletes), uninjured contact sport athletes (same game as mTBI), healthy pre-season contact sport athletes and healthy nonathletes. SA2 will measure the existing N=10 mTBI markers in whole saliva samples from SA1 using two orthogonal, previously validated laboratory saliva immunoassays. ROC analysis will determine diagnostic accuracy of the saliva markers for acute mTBI. Logistic regression at 95% CI will determine prognostic accuracy of the markers for PPCS and RTP at T1-T3. Expected outcomes: Representative and large sample size (180 children across school age, sex, mTBI mechanism and geography) will provide statistically significant, generalizable clinical data. Orthogonal laboratory assays will provide cross-validated, quantitative biomarker data. Demonstration of technical feasibility in SA2 will provide GO criteria for a full biomarker validation and device development in Phase II. If successful, the project has potential for high impact on TBI management in children by providing novel fluid biomarkers for mTBI diagnostics, and offering new insights into pathophysiology of pediatric mTBI. Objective mTBI diagnostics is a key element for making decisions about return-to-play and learning, preventing second impact syndrome and advancing TBI treatment. The proposed rapid saliva mTBI test for children has a strong commercial potential based on no competition and existing team of proven industry partners.PROJECT NARRATIVE Saliva biomarkers for noninvasive diagnostics of acute mTBI in children Pediatric mild TBI (mTBI) is a global health concern. However, there is no objective approach to diagnose pediatric mTBI. The ultimate goal of this SBIR project is to develop a rapid commercial test for objective noninvasive diagnostics of mTBI in children.