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Long-studied protein could be a measure of traumatic brain injury

July 13, 2020

Scientists at the Walter Reed Army Institute for Research (WRAIR) have recently demonstrated that cathepsin B, a well-studied protein important to brain development and function, can be used as biomarker, or indicator of severity, for traumatic brain injury.

Traumatic brain injury (TBI) or brain trauma results from blows to the head, leading to life-changing disruption of the brain and a cascade of long-term health conditions. A leading cause of disability and death worldwide, TBI may occur due to an open-skull injury, like a gunshot wound, a fall, or an automobile accident. Athletes, the elderly, children, and military service members are particularly vulnerable.

Biomarkers are a source of great interest to researchers due to their potential to dramatically improve both the diagnosis and categorization of severity of TBI. Furthermore, they have the potential to validate treatment strategies by indicating whether drugs have reached their proposed targets and achieved therapeutic benefits.

In their publication in the Journal of Neurotrauma, the researchers showed that levels of cathepsin B were increased in areas of the injured brain relevant to controlling the senses, language, memory and other critical executive functions. In healthy cells, cathepsin B has a range of roles, including helping to eliminate damaged cells, maintaining metabolic homeostasis, and degrading improperly produced proteins. When the level of cathepsin B is not tightly controlled, it is linked to inflammation and tissue death. This publication reports the first results demonstrating the ability to use cathepsin B as a blood-based biomarker to capable of identifying TBI severity within different brain regions as well as cerebral spinal fluid.

"Biomarker tests that accurately reflect the extent and severity of injury can dramatically improve the standard of care, minimizing the need for resource-intensive diagnostics like CT or MRI scans in favor of more portable tests," said Dr. Angela Boutte, lead author and section chief of molecular biology and proteomics within the Brain Trauma Neuroprotection Branch at WRAIR. "This would allow for early, accurate detection of TBI, whether at the side of the road after an accident or, most importantly, on the battlefield to help guide medical decisions."

Future research is planned to further characterize the role of cathepsin B in TBI.
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About the Brain Trauma Neuroprotection Branch and the Walter Reed Army Institute of Research (WRAIR)

Dr. Deborah A. Shear is the director of the Brain Trauma Neuroprotection (BTN) Branch, which is part of the Center for Military Psychiatry and Neuroscience at WRAIR. The primary mission of the BTN program is to develop ground-breaking solutions to mitigate the effects of TBI at the point of injury to reduce morbidity and mortality. Providing field-based options for diagnostics, preventative strategies, and treatments are critical to Soldiers. Since 1893, the Walter Reed Army Institute of Research (WRAIR) has been a leader in solving the most significant threats to Soldier readiness and lethality such as disease and battle injury. WRAIR's broad research capabilities at its Washington, D.C., area and expeditionary laboratories function in concert to afford Soldiers the best medical protection and support possible before, during, and after deployment by addressing both longstanding and emerging threats. Though WRAIR's research is focused on Soldier health, its products have important civilian applications, saving countless lives around the world. For more information, visit https://www.wrair.army.mil.

About ALSP Inc.

Dr. Gregory Hook, JD, PhD, is the vice-president and co-founder of American Life Science Pharmaceuticals (ALSP), a privately held company based in San Diego, California, USA, developing small molecule drugs for treating neurological conditions, initially focused on traumatic brain injury (TBI). ALSP's drug development approach is to focus on proprietary inhibitors of papain-like cysteine proteases. Mounting evidence shows that one such protease, cathepsin B, inappropriately increases and redistributes in response to TBI and other neurological conditions resulting in the activation of the inflammasome and triggering severe inflammation, apoptotic and necrotic cell death, and vascular damage. ALSP believes these pathways constitute the pathology of neurological conditions and that ALSP's cysteine protease inhibitors will suppress these pathways and thereby be effective therapeutics. For more information visit http://www.alspinc.com.

About University of California, San Diego

Dr. Vivian Hook is Distinguished Professor of Pharmaceutical Sciences and Neurosciences at the University of California, San Diego. Dr. V. Hook is principal investigator of numerous NIH grants on synaptic neurotransmission in neurodegenerative diseases including traumatic brain injury. The laboratory of Dr. Hook investigates protease mechanisms in TBI and brain disorders which can lead to novel drug targets for therapeutics discovery and development.

About University of Florida

Dr. Kevin K. W. Wang, is the director for Neurotrauma, Neuroproteomics & Biomarkers Research. Dr. Wang is also principal investigator of the VA Merit Award and is Health Research Scientist at Malcom Randall VA Medical Center (Gainesville, FL) where he focuses on advancing Veteran-relevant medical research, as well as improving patient care, management and treatment options.

Walter Reed Army Institute of Research

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