Quadrant Biosciences is developing a new diagnostic to aid in the clinical detection of mild traumatic brain injury (mTBI) in school-aged children and young adults (1322 years). Based on salivary microRNA (miRNA) biomarkers, Quadrants diagnostic will provide an accurate, objective, and non-invasive method for mTBI diagnosis. Such a method is critically needed, as the number of pediatric mTBIs is on the rise, and the developing brains of young patients are more vulnerable to the after-effects of mechanical forces, leading to a wide range of negative effects on physical, cognitive, and psychological function. The diagnosis and assessment of mTBI in adolescents are challenging and rely on subjective measures, leading many mTBIs to go undiagnosed or underreported. This results in suboptimal post-injury treatment and patient management. A biologic assay to accurately diagnose adolescent mTBI would therefore provide an invaluable guide for clinical care, potentially guiding decisions for imaging, return to play, return to school, and therapeutic interventions. While a number of potential biomarkers for objectively detecting mTBI have been proposed, including the blood biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin c-terminal hydrolase (UCH-L1), recent research questions the ability of blood-based biomarkers to differentiate patients with mTBI from those with acute orthopedic trauma, particularly in pediatric populations. Moreover, these assays require venipuncture expertise that is not always available, particularly in the case of sports-related concussions, which account for nearly 1/3 of mTBIs in this patient population. To address these shortcomings, Quadrant Biosciences is creating a novel, objective diagnostic tool based on a panel of saliva miRNA biomarkers that are differentially expressed in patients with mTBI. Pilot studies in over 200 individuals with mTBI have identified a panel of saliva miRNAs capable of diagnosing mTBI and predicting symptom duration. In the proposed Fast Track project, Quadrant will advance development of this test by establishing a rapid, accurate method for quantifying these miRNAs and refining/validating a diagnostic algorithm to differentiate adolescents and young adults with mTBI from peers with symptomology that mimics mTBI (e.g. chronic headaches, anxiety/depression, ADHD, exercise-related fatigue, and orthopedic injury). In Phase I, Quadrant will refine a diagnostic algorithm for mTBI using a rapid quantification technique for saliva miRNAs. Machine learning will be used to develop a diagnostic algorithm that employs miRNA levels from the rapid multiplex assay alongside participant medical and demographic characteristics to predict mTBI status. In Phase II, Quadrant will validate the diagnostic algorithm for differentiating mTBI from medical conditions with overlapping symptomology in a prospective, case-control study of 2500 adolescents and young adults (age 1322 years) to refine the saliva-based diagnostic aid for mTBI. Ultimately, Quadrants proposed salivary miRNA-based test will yield a minimally invasive, objective, biologic test that can aid diagnosis of mTBI, including among patients with confounding psychologic conditions.
Public Health Relevance Statement: Narrative - Children and adolescents account for approximately 2/3 of the 3 million concussions that occur in the U.S. each year, placing them at risk for negative impacts on physical, cognitive, and psychological function, including poor academic performance, behavior, social interactions, and reduced subsequent employment. Unfortunately, mild traumatic brain injury (mTBI) is underdiagnosed due to the poor sensitivity of conventional methods (neurological assessment, self-reporting, imaging, etc.) and lack of an objective, non-invasive diagnostic tool. Quadrant Biosciences rapid, accurate, objective aid for the diagnosis of mTBIs in adolescents and young adults will enable timely and accurate decision-making in mTBI assessment, resulting in reduced re- injury/morbidity, individualized patient management, and improved long-term patient outcomes.
Project Terms: accurate diagnosis; Acute; Address; Adolescent; Adolescent and Young Adult; Advanced Development; Age; age group; aging population; Algorithms; Anxiety; Attention deficit hyperactivity disorder; base; Behavior; Behavioral; Biological; Biological Assay; Biological Markers; Biological Sciences; Biological Testing; Blood; blood-based biomarker; Brain; Brain Concussion; Case-Control Studies; Characteristics; Child; Childhood; Chronic; Chronic Headaches; Clinical; clinical care; Cognitive; concussive symptom; Custom; Databases; Decision Making; design; Detection; Development; Diagnosis; Diagnostic; diagnostic panel; Diagnostic tests; differential expression; Emergency department visit; Employment; Exercise; Fatigue; Glial Fibrillary Acidic Protein; Headache; Image; Imaging technology; improved; Individual; Injury; Machine Learning; Magnetic Resonance Imaging; Measurement; Measures; mechanical force; Medical; Mental Depression; Methods; microRNA biomarkers; MicroRNAs; mild traumatic brain injury; minimally invasive; Morbidity - disease rate; Neurologic; noninvasive diagnosis; novel; novel diagnostics; Olfactory Nerve; Oral cavity; Orthopedics; Participant; patient population; Patient Self-Report; Patient-Focused Outcomes; Patients; Pattern; pediatric patients; peer; Performance; personalized management; Phase; Phenotype; Physical activity; Pilot Projects; Play; Population; potential biomarker; Prospective Studies; Protein C; psychologic; Reporting; Research; Risk; Risk-Taking; RNA Sequences; Saliva; Salivary; Sampling; School-Age Population; Schools; Severities; Social Interaction; Sports; Symptoms; Techniques; Test Result; Testing; Therapeutic Intervention; Time; tool; transcriptome sequencing; Trauma; ubiquitin C-terminal hydrolase; Venipunctures; young adult
