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March 31, 2015
Marriot Marquis, Washington, DC
The Sports and Health Research Program (SHRP) is a public-private partnership of the National Institutes of Health (NIH), the Foundation for the NIH (FNIH) and the National Football League (NFL), aimed at addressing major public health issues related to sports participation and other activities involving repetitive head injuries. Launched in 2012, SHRP was made possible by a $30 million commitment from the NFL with an initial focus on traumatic brain injury (TBI) and plans to investigate other areas of research on serious medical conditions prominent in athletes and relevant to the general population. To date, SHRP has supported three Requests for Applications (RFAs), and in December 2013, announced the selection of eight projects to receive support to answer some of the most fundamental problems on TBI, including understanding the long-term effects of repeated head injuries and improving diagnosis for concussions.
On March 31, 2015, 39 scientists and clinicians attended a meeting at the Marriot Marquis in Washington, DC to review current SHRP projects, receive an update on a longitudinal clinical study, and discuss pilot projects on sports-related brain injury. Organized by Patrick Bellgowan, PhD from the National Institute of Neurological Disorders and Stroke (NINDS), and Stephanie James, Ph.D., Director of Science for the FNIH, the meeting brought together experts in concussion, TBI and chronic traumatic encephalopathy as well as stakeholders from sports and military interests. The March 31st SHRP meeting marked the first time SHRP stakeholders have been able to meet with grantees and hear about their research first-hand. In attendance were representatives from the NFL, National Hockey League, Fédération Internationale de Football Association (FIFA), United States Olympic Committee, National Intrepid Center of Excellence, Companions in Courage Foundation, and Abbott Diagnostics, as well as representatives from several NIH Institutes and FNIH.
NIH Investment in TBI Research
TBI research at NIH encompasses the full range of TBI severity, from mild (concussion) through severe TBI (car crash or serious fall). NIH funded $87 million of research on TBI in FY 2014, with NINDS contributing approximately 60 percent of these funds. The National Institute on Child Health and Human Development (NICHD) supports research on pediatric TBI and coordinates NIH rehabilitation research through the National Center for Medical Rehabilitation Research. As part of an international initiative for TBI research (InTBIR) aimed at lessen the global burden of TBI by 2020, NIH is currently funding two large TBI clinical research programs in the United States to collect data to determine what treatments work best for which patients with TBI. One of these, Approaches and Decisions in Acute Pediatric TBI (ADAPT) focuses on treatment effectiveness in 1000 children with severe TBI, while the other, Transforming Research and Clinical Knowledge in TBI (TRACK-TBI ) focuses on effective treatments in 3000 adults with TBI across the spectrum of injury severity. NINDS also supports the Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System, a $10 million project funded by the Department of Defense (DOD) to build a central inter-agency repository for sharing data to promote collaboration, accelerate research, and advance knowledge on the characterization, prevention, diagnosis and treatment of TBI. Together with DOD and the Uniformed Services University of the Health Sciences (USUHS), NINDS found the Center for Neuroscience and Regenerative Medicine (CNRM ), a collaborative federal intramural research program that brings together clinicians and scientists across disciplines to catalyze innovative approaches to TBI research.
Concussion: The Scope of the Issue
Although concussions are the most common type of TBI, little is known about what happens in the brain at the time of concussion. A concussion can be defined as a sudden change in neurologic function that occurs immediately after the brain encounters a mechanical force. A variety of symptoms accompany concussion including loss or alteration in consciousness, headache, cognitive impairment, behavioral changes, dizziness, and sleep disturbances. When these symptoms persist for more than three weeks, patients are said to suffer from post-concussive syndrome.
Another mystery surrounding the pathophysiology of concussion includes why repetitive concussions increase one’s chances of having worsened and longer duration symptoms upon subsequent concussive episodes. Repeated concussion has also been associated with a degenerative disorder, known as chronic traumatic encephalopathy (CTE). Diagnosis of CTE can only be done post-mortem and is characterized by cerebral atrophy and multi-focal aggregation of the tau protein in neurons and astrocytes around blood vessels near the basin of cortical sulci. While there appears to be an intermediate stage leading up to CTE where tau deposition begins to become confluent in multiple brain regions, it is not clear whether this is associated with a clinical syndrome and what causes these sequelae to progress.
The pathophysiology of concussion is a dynamic process, and key questions remain to be solved, including:
Collaborative Agreements (U01 grants) on CTE and Delayed Effects of TBI:
Neuropathology and Neuroimaging Correlation
Most attention in TBI research has focused on acute care and short-term outcomes for people hospitalized for moderate-severe TBI. Much less is known about the late effects of moderate-severe TBI, and even less about the late effects of mild TBI. In March 2013, NIH released a Request for Applications and selected two four-year projects, each funded at $6 million, aimed at studying the neuropathology associated with CTE and the delayed effects of TBI in order to identify neuroimaging signatures of the neuropathology as a foundation for the development of in vivo diagnostic tools.
Wayne Gordon, Ph.D., Professor and Vice Chair of the Brain Injury Research Center of Mount Sinai , is the principal investigator of the late effects of traumatic brain injury project at the Icahn School of Medicine at Mount Sinai. This study aims to examine TBI as a neurodegenerative condition in non-athletes, and the extent to which the neuropathology overlaps with other degenerative diseases such as CTE and Alzheimer’s disease. By collecting data from two large cohorts, Dr. Gordon and his co-investigators hope to identify uniform behavioral and cognitive information that is linked with pre- and post-mortem imaging and neuropathology. Their study involves:
Ann McKee, M.D., Professor of Neurology and Pathology at the Boston University School of Medicine , leads the Understanding Neurological Injury and Traumatic Encephalopathy (UNITE) study. The UNITE study is a retrospective analysis of professional and amateur athletes, veterans, and other individuals who sustained repetitive TBI before passing away. It aims to establish consensus criteria for the pathological diagnosis of CTE, to validate a pathological staging scheme of CTE severity, to differentiate CTE from other neurodegenerative conditions, and to determine the neuropathology of posttraumatic neurodegeneration after a single TBI. The UNITE study also aims to establish a nationwide brain donation program for TBI to serve as a national resource for TBI biospecimen and data sharing. Progress to date includes:
Pilot Projects on Sports-related Brain Injury
SHRP is currently funding six pilot projects focused on developing new ways to diagnose and treat athletes who suffer concussions. These are up to 2-year projects, collectively funded at approximately $2 million. A brief description of each pilot project and their preliminary findings follow:
Future Directions for SHRP
The stakeholders meeting stimulated a great deal of discussion about the high quality science being done by the SHRP program and what remains missing from the portfolio.