Rapid saliva test for diagnosis of mTBI and prognosis of Persistent Post-conccussion Symptoms (PPCS) in children and adults

Project Summary Rapid saliva test for diagnosis of mTBI and prognosis of Persistent Post-concussion Symptoms (PPCS) in children and adults Mild traumatic brain injury (mTBI) is a leading cause of mortality and morbidity. Children are at a higher risk due to high vulnerability of the immature brain to trauma. mTBI is a significant public health concern because approximately 30% patients develop Persistent Post-concussion Symptoms (PPCS) preventing return to work, school and sports. Current diagnostic methods for mTBI and PPCS are inaccurate due to lack of standard diagnostic criteria. There is unmet need for objective biomarker test. The ultimate goal of this SBIR project is to develop a commercial saliva test for diagnosis of mTBI and prognosis of PPCS. Phase I showed feasibility of the key innovation: saliva biomarkers for diagnosis of mTBI and prognosis of PPCS in children and adults. The proposed Phase II study aims to clinically validate the final biomarker for the commercial test and develop a prototype device showing feasibility of the commercial product. SA1 will collect N=465 serial saliva samples from N=225 adolescent athletes age 11-21 during a multisite prospective cohort study of mTBI, orthopedic injury controls (OI) and healthy controls (HC). mTBI will be diagnosed at ≤72h and PPCS at 30d postinjury. Saliva samples will be collected at ≤72h, 7d and 14d postinjury from mTBI and at enrollment form OI and HC. The proposed sample size will provide rt80% statistical power to obtain statistically significant biomarker data. SA2 will measure 5 candidate biomarkers in N=1063 saliva samples (N=465 samples from SA1 plus N=598 existing samples from ED patients and adult athletes). Statistical modeling of a Training set of subjects (N=475) will down select the final marker and endpoint for the commercial test based on best diagnostic and prognostic performance. The selected marker and endpoint will be validated using a Validation set (N=240) based on ≥90% accuracy, sensitivity and specificity of mTBI diagnosis and PPCS prognosis in children and adults. OI will show mTBI specificity. HC will define normal range of marker concentrations and biological variability. SA3 will develop a prototype lateral flow immunoassay (LFA) for a selected biomarker. Expected Outcomes: Results will rigorously clinically validate the saliva biomarker of mTBI and PPCS for the commercial product. Large and representative sample size (N=715 subjects across mTBI mechanisms of injury, outcome, age, sex and geography) will provide statistically significant, generalizable clinical data. N=1063 serial saliva samples and analytically validated assays will provide accurate and reliable biomarker data. The prototype device will show technical feasibility of the commercial test. Overall, this project has high potential for a wide-ranging impact on TBI care by providing an objective, clinically feasible biological biomarker of mTBI and PPCS, and translating this innovation into a practical tool for clinical use in point-of- care. The proposed product has a strong commercial potential based on a proven and low risk LFA device, achievable FDA path, key opinion leaders committed to clinical adoption, competitive patent portfolio and limited competition.