Cohen Veterans Bioscience is driving the development a Brain Trauma Blueprint to guide a next generation of diagnostics and therapeutics across Traumatic Brain Injury and Post-Traumatic Stress Disorder. In 2019, we hosted our second State of the Science Summit (SOSS) with over 100 thought leaders to foster consensus around potential paths to treatment for TBI. The goal was to define TBI beyond the typical classifications of mild, moderate or severe, in order to more clearly describe underlying disease mechanisms. The Summit focused on the chronic sequelae of TBI and aimed to identify current knowledge gaps in the etiology and mechanisms of persistent TBI symptoms.
The resulting recommendations create actionable research priorities to be prioritized across the research ecosystem and will be rolled out in the next few months.
The Brain Trauma Blueprint is an initiative aimed at accelerating an era of personalized medicine for survivors of brain trauma through a series of invitation-only State of the Science Summits (SoSS). With few FDA-approved treatments for long term neuropsychiatric sequelae of traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD), the development of targeted therapeutics will require clearer understanding of their biological underpinnings. By fostering collaboration across the broader stakeholder community, we will enable translational research gaps to be bridged and achieve solutions sooner for those suffering from trauma-related brain disorders.
Each SoSS includes a review of the landscape drafted by a Scientific Planning Committee, which comprises of key thought leaders with deep expertise in trauma-related brain disorders. The first of the two-day meeting consists of presentations and working sessions discussing the state of the field and major research gaps. The second day includes time to define, refine, and prioritize research gaps.
The trauma-related brain disorder research community has repeatedly lamented the lack of mechanistically targeted therapeutics for TBI. Through breakout and group discussions, consensus around knowledge gaps and strategies to leverage the combined intellectual resources of the scientific and clinical communities will lead to the generation of research priorities that will overcome the gaps and hasten the development of precision-therapeutic options for individuals living with trauma-related brain disorders. This requires advancing knowledge on molecular mechanisms of injury, more refined methods of diagnosis, subtyping patients to better select potential treatments for their disease mechanism, and successfully advancing through clinical trials. A blueprint of past and current research activities can help guide development efforts and accelerate the progression towards a new generation of precision diagnostics and targeted therapeutics.
TBI is currently classified as mild, moderate, or severe and is managed based on a level of consciousness, irrespective of the heterogenic pathophysiology leading to that severity score. The ability of these classifications to predict subsequent patient burden, including neurodegenerative trajectory, is not well understood and can be complicated by subjective measurement techniques, fluctuating presentations and comorbid disorders. Indeed, despite initial hospitalization and inpatient rehabilitation services, about 50% of people with TBI will experience further decline in their daily lives or die within 5 years of their injury; in cases of mild injury where patients often fail to seek help, delayed sequelae may arise leading to cognitive decline or other functional deficits.
While great strides have been made in managing patients after acute brain injuries, particularly those classified as severe, the field is increasingly looking to address the chronic sequelae of mild brain injuries by focusing on identifying the molecular mechanisms underlying the long-term symptoms using animal models2. This requires identifying gaps in our understanding of the presence, presentation, trajectories, and underlying mechanisms of the long-term effects. By leveraging the power of leaders across the brain health spectrum and strengthening the cohesion of the scientific, clinical and patient communities within TBI, the community will have a roadmap to identify the underlying biological processes across TBI injury types, improve patient biotyping and better advance clinical trials. This will translate to precise diagnostics and prognostics for those suffering from brain injuries and ultimately reduce patient burden.
1TBI Model Systems (TBIMS) National Database
The theme of the second State of the Science Summit was Paths to Treatment for Traumatic Brain Injury(s) with a focus on the taxonomy and nosology of the chronic sequelae, challenges and opportunities in clinical practice and development, and etiology and mechanism of persistent symptoms3. As measurement tools advance, research has been able to focus on different types of injury, beyond the mild, moderate, and severe classifications. To augment and support the many efforts across fields and organizations over the past decade, we aim to map a consensus blueprint to drive translational science for TBI.
3Excluding penetrating injury; stroke; acute surgical emergencies
Reviewing the Gaps in Preclinical and Translational Science in Traumatic Brain Injury
Douglas H. Smith, Patrick Kochanek, Susanna Rosi, Retsina Meyer, Chantelle Ferland-Beckham, Eric M Prager, Stephen T. Ahlers, Fiona Crawford
Epidemiology of Chronic Effects of Mild Traumatic Brain Injury
Juliet Haarbauer-Krupa, Mary Jo Pugh, Eric M Prager, Nicole Harmon, Jessica Wolfe, Kristine Yaffe
Phenotyping the Spectrum of Traumatic Brain Injury: A Review and Pathway to Standardization
Mary Jo Pugh, Eamonn Kennedy, Eric M Prager, Jeffrey Humpherys, Kristen Dams-O’Connor, Dallas Hack, Mary Katherine McCafferty, Jessica Wolfe, Kristine Yaffe, Michael McCrea, Adam R Ferguson, Lee Lancashire, Jamshid Ghajar, Angela Lumba-Brown
Biomarker Development to Advance Diagnosis and Treatment of Traumatic Brain Injury
Elisabeth A Wilde, Ina-Beate Wanner, Kimbra Kenney, Jessica Gill, James Stone, Seth Disner, Caroline Schnakers, Andreas Jeromin
Designing Successful Clinical Trials for Traumatic Brain Injury
Lisa A Brenner, Donald G Stein, David Cifu, Allyson Gage, Eric M Prager, David W Wright, Grant Iverson, David L Brody
Implementation Concepts and Strategies to Support the State of the Science Surrounding Traumatic Brain Injury Clinical Care Guidelines
Angela Lumba-Brown, Eric M Prager, Nicole Harmon, Michael McCrea, Michael Bell, Jamshid Ghajar, Scott Pyne, David Cifu
Stephen Ahlers, PhD
Director, Operational and Undersea Medicine Directorate at Naval Medical Research Center
David Cifu, MD
Chairman and Professor at VCU Department of PM&R, National Director for PM&R in Department of Veterans Affairs
Fiona Crawford, PhD
President & CEO, Roskamp Institute
Jam Ghajar, MD, PhD, FACS
President, Brain Trauma Foundation, Clinical Professor of Neurosurgery at Stanford University School of Medicine
Jessica Gill, PhD, RN, FAAN
Deputy Scientific Director of the Division of Intramural Research at the National Institute of Nursing Research
Grant Iverson, PhD
Director, Sports Concussion Program, MassGeneral Hospital for Children; Director, Neuropsychology Outcome Assessment Laboratory, Department of Physical Medicine and Rehabilitation, Harvard Medical School, and Spaulding Rehabilitation Network; Associate Director, Traumatic Brain Injury Program, Home Base, A Red Sox Foundation and Massachusetts General Hospital Program
Michael McCrea, PhD, ABPP
Professor, Neurosurgery and Neurology; Director, Brain Injury Research Program, Medical College of Wisconsin
James Stone, MD, PhD
Vice Chairman of Clinical Research, Associate Professor of Radiology and Medical Imaging, University of Virginia
Elisabeth Wilde, PhD
Associate Professor, Director of Research for Physical Medicine and Rehabilitation, Baylor College of Medicine
Kristine Yaffe, MD
Professor of Psychiatry, Neurology and Epidemiology, Roy and Marie Scola Endowed Chair, Vice Chair of Research in Psychiatry, UCSF