Apyrase: A Portable Treatment to Prevent Burn Progression and Infection
Abstract
Topic Area: This proposal directly addresses the Fiscal Year 2015 Military Burn Research Program Topic Area of Healing Acute Burns with topical treatments. In keeping with the program description, the focus is on applied research that provides the key step toward clinical use. The anti-inflammatory, pro-healing, and antibacterial effects of apyrase, a topical therapeutic, will be optimized for treatment of burn wounds using a well-established and representative large-animal model. The results of this study will establish the safety and efficacy of apyrase, which will provide the basis for translation into human use. Clinical Applications, Benefits, and Risks: Burn injuries are frequent in Wounded Warriors during combat. The extent of burn injury increases following the initial injury due to local thrombosis and tissue necrosis, which is further compounded by infection. The inflammatory response caused by the burn injury and infection can lead to compromise of organ systems throughout the body. Prompt surgery to remove severely burned tissue and skin grafting to cover the wounds is the current definitive treatment, but such treatment may not be feasible in combat zones or austere conditions. Our preliminary data show that topical apyrase, an enzyme that breaks down ATP released from burn damaged tissues, helps to limit inflammation and promote healing when applied early to burn wounds. We have also found that treatment with apyrase decreases bacterial infection of the wound, a dreaded complication observed in severely burned combat casualties. We propose studies in a pig model that closely resembles human burns that aim to (1) demonstrate that apyrase decreases inflammation and wound expansion of partial thickness burns without toxicity and (2) validate the anti-microbial properties of apyrase in partial-thickness burns. Given that this is a topical therapeutic, there are very little risks to its application and preliminary studies have not shown any toxicity. We hypothesize that topical application of apyrase to burn wounds will reduce inflammation, minimize wound progression, and eliminate infection without local toxicity. Projected Timeline: In the first year, we will validate our large animal burn model. In our second year, we will demonstrate the effect of infection on burn wounds in our pig model, and in the final year, we will validate the ability of apyrase to mitigate the infection and improve wound healing. Given that apyrase already has Food and Drug Administration approval and the proposed intervention is through topical treatment, we believe that rapid translation to human trials can begin. Benefit to Service Members and/or U.S. Veterans who have sustained burn injuries as well as families, caregivers, and the general public: We foresee the results from this work having an immediate impact on military, Veteran, and civilian populations by improving outcomes of burn wound injuries by limiting burn wound inflammation, decreasing the risk and severity of infection, and allowing for more rapid wound healing. Specifically, we foresee this topical treatment being deployed to the frontlines and administered immediately on Wounded Warriors due to its ease of application.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610574
Entities
People
- Stewart Wang
Organizations
- United States Army
- University of Michigan