Point-of-Injury Intranasal ALM Drug Therapy to Reduce Secondary Injury and Improve Outcomes After TBI in Civilian and Military Resource-Limited Environments
Abstract
Background: Traumatic brain injury (TBI) is a global epidemic, affecting around 69 million people annually. TBI occurs when a sudden external force injures the brain potentially leading to death or disability. It can occur from a violent blow or a jolt to the head, or from an object penetrating the skull, such as a bullet or explosive fragments. The primary injury leads to secondary injury processes in both the brain and throughout the body including cell swelling and death; immune dysfunction; inflammation; bleeding and clotting derangements; and heart, lung and bowel dysfunction. No safe and effective drug therapy exists to treat mild to severe TBI. On the battlefield, TBI is estimated to be responsible for 20-25% of injuries. Since 2000, TBI has affected >450,000 U.S. military Service Members, including >51,000 moderate- to-severe injuries. These injuries cause difficulties with cognition, learning and sleep, as well as mental disorders such as depression, anxiety, and PTSD. TBI can also lead to later-life cardiovascular disease, as well as dementia and neurodegenerative diseases including Alzheimer s disease and Parkinson’s disease. Our study addresses major unmet needs in both military and civilian settings. Objective and Rationale of the Project: Our objective is to provide the Department of Defense with a new frontline drug therapy to treat TBI in combat and other military settings immediately after the injury has occurred. The drug will prevent early death and further provide protection and stabilization of the casualty for up to 7 days in the field. The idea is to protect the brain and the whole body by reducing secondary injury progression and TBI-associated complications. If secondary injury progression can be reduced, many lives can be saved, military personnel will return to active duty faster, and TBI casualties will have reduced disability and neurodegenerative complications later in life. The aim of the proposed project is to evaluate the survival and protection effects of ALM, a novel neuroprotective drug therapy, in a military-relevant rat model of moderate TBI. We will examine injectable (IV) and nasal (spray) administration which will translate to simple use in austere locations or in civilian prehospital environments. Focus Areas: The focus areas we address in our proposal are: (1) the acute treatment of TBI in rural or other resource-limited environments, and by peers, teams, or first responders/medics; (2) generation of evidence regarding the safety, efficacy, and utility of neuroprotective measures; and (3) interventions that promote sustained recovery and address neurodegenerative processes associated with TBI. Applicability of the Research: Reduce early mortality and morbidity from moderate TBI. Types of Patients: All military personnel, Veterans, their Families, and the civilian population. Potential Clinical Applications, Benefits, and Risks: Early IV or intranasal treatment by first responders or combat medics after suspected TBI will reduce early mortality, secondary injury progression, and TBI- associated whole-body complications. Our small-volume drug therapy will also offer a key tactical advantage because it will simplify treatment of combatants suspected of having TBI and other injuries in the field. In the civilian setting, ALM has broad applications from sport-related concussions, falls and car crashes, to mass casualty events including terrorist bombings. At this stage, we see no risks. Timeline: We expect ALM use in clinical and field situations is feasible within 5-6 years if this award is successful. We would work with our civilian and military colleagues to expedite field use. Impact on Well-Being of Service Members, Veterans, and Military Beneficiaries: This study has the potential to provide the first effective and safe EARLY treatment for TBI, which will improve recovery by reducing TBI-related morbidity such as cardiovascular dysfunct
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310917
Entities
People
- Geoffrey P Dobson
Organizations
- James Cook University
- United States Army