Citation

Kochanek PM, Jackson TC, Jha R, Clark RSB, Okonkwo DO, Bayir H, Poloyac SM, Wagner AK, Empey PE, Conley YP, Bell MJ, Kline AE, Bondi CO, Simon DW, Carlson SW, Puccio AM, Horvat CM, Au A, Elmer J, Treble-Barna A, Ikonomovic M, Shutter L, Taylor DL, Stern AM, Graham SH, Kagan VE, Jackson EK, Wisniewski SR, Dixon CE. J. Neurotrauma 2018; ePub(ePub): ePub.

Affiliation

University of Pittsburgh, Neurosurgery , 3434 Fifth Ave , Pittsburgh, Pennsylvania, United States , PA ; dixonec@upmc.edu.

Copyright

(Copyright © 2018, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2018.6203

PMID

30520681

Abstract

New neuroprotective therapies for severe traumatic brain injury (TBI) have not translated from pre-clinical to clinical success. Numerous explanations have been suggested in both the pre-clinical and clinical arenas. Coverage of TBI in the lay press has reinvigorated interest creating a golden age of TBI research with innovative strategies to circumvent roadblocks. We discuss the need for more robust therapies. We present concepts for traditional and novel approaches to defining therapeutic targets. We review lessons learned from the ongoing work of the pre-clinical drug and biomarker screening consortium Operation Brain Trauma Therapy and suggest ways to further enhance pre-clinical consortia. Biomarkers have emerged that empower choice and assessment of target engagement by candidate therapies. Drug combinations may be needed and it may require moving beyond conventional drug therapies. Precision medicine may also link the right therapy to the right patient including new approaches to TBI classification beyond the Glasgow coma scale or anatomical phenotyping-incorporating new genetic and physiologic approaches. Therapeutic breakthroughs may also come from alternative approaches in clinical investigation (comparative effectiveness, adaptive trial design, use of the electronic medical record, big data). The full continuum of care must also be represented in translational studies, given the important clinical role of pre-hospital events, extra-cerebral insults in the ICU, and rehabilitation. TBI research from concussion to coma can cross-pollinate and further advancement of new therapies. Misconceptions can stifle/misdirect TBI research and deserve special attention. Finally, we synthesize an approach to deliver therapeutic breakthroughs in this golden age of TBI research.

Language: en

Keywords

CLINICAL TRIAL; HEAD TRAUMA; REHABILITATION