Alignment with PRMRP Topic Areas: The proposed work is directly in line with the overarching vision of the FY20 PRMRP to improve the health and well-being of all military Service Members, Veterans, and beneficiaries. The proposal addresses the following PRMRP Topic Area of Musculoskeletal Health, with a specific focus on “Research to better understand tissue-specific diseases or injuries (e.g., bone, cartilage, tendon, and/or muscle) with a focus on treatment, recovery, or regeneration.” The proposed work seeks to evaluate SP16, a synthetic peptide derived from a naturally occurring serine protease inhibitor (SERPIN), Alpha-1 Antitrypsin (AAT), as an immunomodulatory therapeutic for use in the treatment of Volumetric Muscle Loss (VML).

VML is a type of combat injury that results in massive loss of skeletal muscle such that the injured person may never be able to function in the same way again due to permanent loss of strength and dexterity. Therefore, it is of extreme interest to develop treatments for this type of injury that can regrow the essential components of the injured muscles in the body such that strength and dexterity are sufficiently restored to enable return to duty of the Wounded Warrior and ultimately a greater quality of life during and after their service. Unfortunately, the best available treatments for regrowing these injured muscles are limited from completely healing the injury by the body’s immune system and inflammatory response. As such, one approach to encourage regrowth of muscle is the application of agents that augment so that the treatments that produce new muscle can function better. A new agent, SP16, has been developed that shows potential for modulating the immune-inflammatory response and may be the necessary key to unlocking our ability to treat this type of combat injuries. As such, we are proposing to determine how well the agent is able to control the immune-inflammatory response to VML and whether this action has positive downstream effects on leading clinically available treatments for growing new muscle. If successful, the study will represent a significant advance in the treatment of VML injuries with the potential to revolutionize the way we care for our wounded Service Members, and promote increased readiness of our armed forces.