Principle Investigator: John Elfar, MD, FACS
Performing Organization: University of Arizona
Background: Severe wound and burn injuries are notoriously difficult to treat, and most available treatments aim to debride dead tissue, prevent infection, and replace fluid losses. Once dead tissue is gone, surgeons cover large skin defects with grafts before infection or desiccation destroys deeper tissue. The main goal of modern wound and burn treatment seems to be to delay the consequences of open wounds as opposed to speeding skin regeneration. Current treatments do not increase the regenerative potential of either skin grafts or the remaining uninjured skin. Actual regenerative treatments would transform treatment in civilians and warfighters in combat zones.
Current Research Efforts: Much of wound research is also geared towards preventing complications as opposed to regenerative treatments, few of which are ready for translation to human trials. Most of the pipelines for future treatment involve long development timelines and still focus chiefly on infection control instead of driving tissue to regenerate and heal faster. This reality is not likely to change quickly because many promising burn treatments in the pipeline are neither forward deployable nor translatable with clinical trials right now. A significant gap is the need for a forward-deployable regenerative burn treatment that can be trialed now. The best treatment allows for early use in both civilian and military burn patients as an addition to current protocols.
Strategic Challenges: The current strategic challenges for the United States Department of Defense (DoD) hinge on the delivery of advanced medical care at the point of injury. Future conflicts will likely force the DoD to operate in a disbursed and decentralized manner against sophisticated nation-state threats that will create an all-domain contested environment. Military units will operate deep behind multiple threat umbrellas from enemy anti-air, anti-ship, and surface-to-surface fire systems, creating problems of contested air and sea space. This will prevent the timely medical evacuations that were routine for the past two decades of conflict in Iraq, Afghanistan, and Syria. Units previously able to evacuate personnel within minutes of injury will, in the future, endure days of temporary isolation before combat casualties can be evacuated from the battlefield. Recent developments in the Russia-Ukraine conflict also demonstrate a much greater use of explosive artillery, including incendiary munitions that cause higher civilian and military burn casualty rates. These combined factors will encumber logistics forces, medical units, and personnel stretched across vast distances.
Confronted with such dilemmas, we must immediately deploy the highest level of care at the point of injury. The best treatments are readily available at the lowest level of care, without requirements for powered storage (i.e., refrigeration) or sanitized conditions. The optimal solution should not require heavy equipment or advanced expertise. This is a problem uniquely suited for drug repurposing.
Proposed Technology. We found that 4-aminopyridine (4-AP), an already FDA-approved treatment for multiple sclerosis (MS) accelerates healing of full-thickness burns and wounds in animals. Many forms of 4-AP will be available in the future for burn and wound treatments, but the critical path forward is to trial 4-AP now. Oral regenerative wound and burn treatment is a first step that we can trial today.