SESSION TITLE

Discovery and Validation of Novel Biomarkers for Preclinical TBI  TEAM

DESCRIPTION

The TOP-NT Consortium was developed to address the bi-directional translational gap between preclinical and clinical research in TBI with a mission to develop and validate pathophysiologically based preclinical outcome measures or functional markers that align closely with practical clinical assessments in TBI and to enable the harmonization and sharing of preclinical research data. Recently, federal funding agencies have encouraged and supported efforts to harmonize data collection in preclinical neurotrauma research. For example, a set of preclinical CDE are currently available that were developed to improve transparency in preclinical reporting of animal characteristics, injury mechanism, and behavioral outcomes for preclinical TBI research. However, data collection and reporting harmonization is only a first step toward improved translation between preclinical and clinical TBI. While existing animal models mimic the injury causes, difficulties in translating promising therapeutics are exacerbated by the lack of alignment of discrete measures of the underlying injury pathology between the animal models and human subjects. Translational activities in this area largely rely on gross behavioral tests and outcomes of efficacy that correlate with injury severity in the animal models, but do not mimic practical and objective clinical measures of the underlying pathology that could facilitate patient selection or stratification for clinical trial design. Ultimately, the multi-site TOP-NT Consortium will develop, validate, and distribute new functional markers of TBI pathophysiology and provide an infrastructure model that establishes an open science approach for preclinical data collection, curation and sharing strategies that will enable broad access to methodologies and datasets developed.

EDUCATIONAL OBJECTIVES

At the conclusion of this session, attendees will be able to:

1. Learn about the availability of existing and future resources developed to enhance transparency and translation in the area of preclinical neurotrauma.
2. Acquire information about novel preclinical neuroimaging approaches that are being developed and validated in the TOP-NT Consortium, how these neuroimaging methods are associated with specific pathophysiological mechanisms of TBI, and the processes developed for coordinating and calibrating preclinical neuroimaging across multiple imaging centers.
3. Learn which biofluid markers or sets of markers are being tested and how they are being proposed to characterize specific pathophysiological mechanisms in TBI. Further, they will become informed about the development and availability of standard operating procedures for the collection, storage, and analysis of preclinical biofluids in a multisite consortium.
4. Gain knowledge of the TOP-NT model for data sharing and the utility of multivariate analytic methods that can be applied when multiple preclinical research datasets are procedurally aligned and shared.