CONTACT US: Contact info
|
Citation |
Kochanek PM, Dixon CE, Mondello S, Wang KKK, Lafrenaye A, Bramlett HM, Dietrich WD, Hayes RL, Shear DA, Gilsdorf JS, Catania M, Poloyac SM, Empey PE, Jackson TC, Povlishock JT. Front. Neurol. 2018; 9: e640. |
|
Affiliation |
Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, United States. |
|
Copyright |
(Copyright © 2018, Frontiers Research Foundation) |
|
DOI |
|
PMID |
30131759 |
|
PMCID |
|
|
Abstract |
Current approaches have failed to yield success in the translation of neuroprotective therapies from the pre-clinical to the clinical arena for traumatic brain injury (TBI). Numerous explanations have been put forth in both the pre-clinical and clinical arenas. Operation Brain Trauma Therapy (OBTT), a pre-clinical therapy and biomarker screening consortium has, to date, evaluated 10 therapies and assessed three serum biomarkers in nearly 1,500 animals across three rat models and a micro pig model of TBI. OBTT provides a unique platform to exploit heterogeneity of TBI and execute the research needed to identify effective injury specific therapies toward precision medicine. It also represents one of the first multi-center pre-clinical consortia for TBI, and through its work has yielded insight into the challenges and opportunities of this approach. In this review, important concepts related to consortium infrastructure, modeling, therapy selection, dosing and target engagement, outcomes, analytical approaches, reproducibility, and standardization will be discussed, with a focus on strategies to embellish and improve the chances for future success. We also address issues spanning the continuum of care. Linking the findings of optimized pre-clinical consortia to novel clinical trial designs has great potential to help address the barriers in translation and produce successes in both therapy and biomarker development across the field of TBI and beyond. Language: en |
|
Keywords |
biomarker; drug screening; neuroprotection; pre-clinical consortium; reproducibility; rigor; target engagement; theranostic |