Bioanalysis Director Center for Neuroscience and Regenerative Medicine, HJF Bethesda, Maryland
Abstract Text: The failures of previous clinical trials in treating the heterogeneous disorders related to traumatic brain injury (TBI) highlight the importance of patient stratification by underlying physiology. Furthermore, there remains a need for discovery of new therapeutic targets and the measurement of target engagement and pharmacodynamic effect. These well-recognized gaps require the discovery and development of meaningful biomarkers. Since its inception, the Center for Neuroscience and Regenerative Medicine (CNRM) at the Uniformed Services University has provided biorepository services for the purpose of biomarker analysis and discovery. Recently, CNRM has expanded the capabilities of the repository to establish a Biomarkers Core, capable of both storage and analytic services. By investing in innovative high-throughput molecular biology platforms such as the Quanterix Single Molecule Array (Simoa), Meso Scale Discovery, and omics platforms such as the NanoString for biomarker discovery, CNRM is prepared to facilitate execution of TBI-related CNRM-sponsored research projects with samples stored in the CNRM Biorepository and approved externally funded projects. Furthermore, CNRM is further developing the brain biopsy from a blood test concept by isolating brain-derived extracellular vesicles (bEVs) from plasma and serum samples and will be adding digital array-based proteomics capabilities for unbiased discovery. Our preliminary study results indicated that the novel bEV isolation methods greatly enrich neuron and/or microglia-derived EVs, which significantly facilitate neuronal and inflammatory biomarker profiling representing events in their origins. These capabilities will enhance the study of biomarker signatures for the study of axonal injury, astrogliosis, microgliosis and other signatures of neuroinflammation, and waste clearance mechanisms such as the glymphatic system, which may be related to the injury and recovery progress in TBI and related symptoms. The new biomarker study platforms in CNRM will greatly expand our research breadth and depth, most importantly, increase our study specificity in evaluating brain injury in military service members and improving the care for their recovery. The aim of our presentation is to demonstrate our strength in both biorepository and biomarker analysis in potential collaborations of TBI biomarker research.