Discovering the First Biomarker for Brain Injury
Although breakthroughs in science and medicine happen every day, most discoveries may not be "exciting" enough to be considered front-page news. However, the U.S. Army Medical Materiel Development Activity's Neurotrauma and Psychological Health Project Management Office recently announced a breakthrough that certainly warrants wide dissemination – worldwide, in fact. In conjunction with its commercial partner Banyan Biomarkers, Inc., the NPH PMO has received U.S. Food and Drug Administration approval to market the first-ever blood test, the Banyan BTI™ (Brain Trauma Indicator), used to evaluate instances of mild traumatic brain injury.
The current product is a serum-based assay that isolates two particular proteins, or biomarkers, released upon injury to the brain. This unique data is analyzed as part of a clinical assessment, within 12 hours of injury, to assist in determining if a computed tomography scan of the head is necessary or may be ruled out. Ruling out CT scans in certain instances can save patients from needless radiation exposure, while also eliminating both the potential harm and costs associated with the procedure.
For the better part of the past 15 years, the Laboratory Assay for Traumatic Brain Injury acquisition program has been a prime focus of Army Medicine, charged to the U.S. Army Medical Research and Materiel Command, Fort Detrick, Maryland, for its management and oversight. As a lifecycle management command, the USAMRMC has been involved with this effort since its inception, from the early stages of scientific research through its clinical testing to subsequent fielding.
As NPH PMO project manager, Army Lt. Col. Kara Schmid is closely tied to the LATBI effort, having been involved with this critical program for more than a decade, and she remains highly invested in the success of TBI research.
"TBI is not just a military problem," said Schmid. "Brain injury, both in the military and civilian populations, is a significant problem that takes a substantial toll – both physically and financially – on those affected by it. A blood test that is fast, affordable and easy to use is necessary to help solve this problem."
Introduced to this study in 2006 as deputy director of USAMRMC's Combat Casualty Care Research Program, who initially funded the project, Schmid helped to establish the LATBI Integrated Product Team. In 2009, she began a five-year assignment at Walter Reed Army Institute of Research, where she served as technical product manager for TBI acquisition products. In this role, Schmid led the LATBI IPT and supervised the acquisition strategy for the LATBI biomarkers effort, which reached a Milestone B mark during this time. After gaining valuable insight during one year at the U.S. Food and Drug Administration, Schmid joined USAMMDA as TBI product manager, and since 2016 has served as NPH PMO project manager.
Given her close connection to the LATBI program, Schmid is quite proud of its recent triumph, which includes the largest clinical trial ever conducted for TBI biomarkers. She believes the success of the effort is due primarily to the involvement of many USAMRMC team members that have championed the project since its beginning.
"As a lifecycle management command, our people are dedicated to product development from start to finish," said Schmid. "In this case, from the preclinical studies by WRAIR and the University of Florida to the early science and technology research managed by the Combat Casualty Care team, to advanced development at both USAMMA [U.S. Army Medical Materiel Agency] and USAMMDA. The level of personal investment is high because the result could help tackle the difficult problem of TBI throughout our military, and civilian, populations."
During a training seminar held recently at Fort Detrick, the TBI assay process was demonstrated for a select group of military scientists and researchers involved with the program. The current assay uses a dedicated benchtop device for analysis, the BioTek Synergy™2 microplate reader, which takes about four hours to complete. However, the ultimate goal is to create a small handheld unit that can be used anywhere, including the battlefield, and provide test results in minutes. Not only would a faster diagnosis help to save lives, it could also eliminate the evacuation of military personnel to military treatment facilities for unnecessary CT scans. The LATBI team remains hopeful this smaller unit could be realized within a few years.
According to USAMMDA's commercial partner, future plans for the product are focused on making the test easier and faster to run, so that more physicians can obtain information on their patients in a much shorter timeframe. Additional improvements include modifying the assay so it may be used on a wide range of instruments throughout the world.
While these updates to the product and its dedicated device remain on the short list of future enhancements, Schmid continues to look beyond to other applications the assay may serve.
"We call this Version 1.0, because we're anticipating updates, but we'd also like to see what else the assay can do for TBI," she said. "Ruling out a CT scan is just the first indication, but could the markers predict recovery as well? Is the level of marker linked to the severity of injury – the worse the injury, the higher the marker?"
Schmid explained the team will move forward prospectively, collecting data on how the assay performs in various circumstances. With an established dataset, they can create specific clinical trials to test for potential new indications that may provide critical answers regarding TBI.
As the premier developer of world-class military medical capabilities, USAMMDA has helped to revolutionize Army medicine through successful partnerships with commercial companies, and this LATBI effort remains a clear example of effective collaboration.
"Throughout our entire working relationship, our commercial partner has been very cooperative and flexible with requests from the Department of Defense," said Schmid. "Over the past 15 years, despite some obstacles, they never gave up on this project – and now they're able to enjoy the success we're seeing."
Going forward, the LATBI program certainly has the potential to unlock numerous other mysteries related to brain injury. As the current assay utilizes only two biomarkers for analysis, a pipeline of other TBI biomarkers remain to be studied, and these may be used to identify and classify indications perhaps still unknown to the current field of research.
For now, however, the LATBI team certainly has earned the right to pause and consider its accomplishments thus far. With this product, there are plateaus yet to be reached, new discoveries still to be realized, and numerous lives potentially to be saved. Fortunately, the group holds two of the most important ingredients for success, hope and perseverance, which should continue to carry this project far into the future.