Paths to Successful Translation of New Therapies for Severe Traumatic Brain Injury in the Golden Age of Traumatic Brain Injury Research: A Pittsburgh Vision
Authors
Patrick M. Kochanek, Safar Center for Resuscitation Research, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Travis C. Jackson, Safar Center for Resuscitation Research, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Ruchira M. Jha, Safar Center for Resuscitation Research, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.Follow
Robert S. Clark, Safar Center for Resuscitation Research, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
David O. Okonkwo, Department of Neurological Surgery, UPMC Presbyterian Hospital, Pittsburgh, Pennsylvania, USA.
Hülya Bayır, Safar Center for Resuscitation Research, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Samuel M. Poloyac, Safar Center for Resuscitation Research, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Amy K. Wagner, Safar Center for Resuscitation Research, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Philip E. Empey, Safar Center for Resuscitation Research, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Yvette P. Conley, Health Promotion and Development, University of Pittsburgh School of Nursing, Pittsburgh, Pennsylvania, USA.
Michael J. Bell, Department of Critical Care Medicine, Children's National Medical Center, Washington, DC, USA.
Anthony E. Kline, Safar Center for Resuscitation Research, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Corina O. Bondi, Safar Center for Resuscitation Research, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Dennis W. Simon, Safar Center for Resuscitation Research, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Shaun W. Carlson, Safar Center for Resuscitation Research, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Ava M. Puccio, Department of Neurological Surgery, UPMC Presbyterian Hospital, Pittsburgh, Pennsylvania, USA.
Christopher M. Horvat, Safar Center for Resuscitation Research, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Alicia K. Au, Safar Center for Resuscitation Research, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Jonathan Elmer, Departments of Emergency Medicine and Critical Care Medicine, University of Pittsburgh School of Medicine, UPMC Presbyterian Hospital, Pittsburgh, Pennsylvania, USA.
Amery Treble-Barna, Safar Center for Resuscitation Research, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Milos D. Ikonomovic, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Lori A. Shutter, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
D Lansing Taylor, University of Pittsburgh Drug Discovery Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Andrew M. Stern, Drug Discovery Institute, Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Steven H. Graham, Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA.
Valerian E. Kagan, Department of Environmental and Occupational Health, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Edwin K. Jackson, Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Stephen R. Wisniewski, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, USA.
C Edward Dixon, Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
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, and big data). The full continuum of care must also be represented in translational studies, given the important clinical role of pre-hospital events, extracerebral insults in the intensive care unit, 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.
Medical Subject Headings
Animals; Brain Injuries, Traumatic (drug therapy); Humans; Neuroprotective Agents (pharmacology); Translational Research, Biomedical
Publication Date
11-15-2020
Publication Title
Journal of neurotrauma
Digital Object Identifier (DOI)
10.1089/neu.2018.6203
Recommended Citation
Kochanek, Patrick M.; Jackson, Travis C.; Jha, Ruchira M.; Clark, Robert S.; Okonkwo, David O.; Bayır, Hülya; Poloyac, Samuel M.; Wagner, Amy K.; Empey, Philip E.; Conley, Yvette P.; Bell, Michael J.; Kline, Anthony E.; Bondi, Corina O.; Simon, Dennis W.; Carlson, Shaun W.; Puccio, Ava M.; Horvat, Christopher M.; Au, Alicia K.; Elmer, Jonathan; Treble-Barna, Amery; Ikonomovic, Milos D.; Shutter, Lori A.; Taylor, D Lansing; Stern, Andrew M.; Graham, Steven H.; Kagan, Valerian E.; Jackson, Edwin K.; Wisniewski, Stephen R.; and Dixon, C Edward, "Paths to Successful Translation of New Therapies for Severe Traumatic Brain Injury in the Golden Age of Traumatic Brain Injury Research: A Pittsburgh Vision" (2020). Neurology. 1356.
https://scholar.barrowneuro.org/neurology/1356
