Granexin to Prevent Injury Progression and Optimize Healing Outcome of Acute Burns
Abstract
Military trauma resulting from blast injury and war-related burn casualties can result in wounds associated with large areas of cutaneous fibrosis (scarring). Burn progression results in secondary necrosis and increases in the likelihood of tissue loss, hypertrophic scarring, and patient morbidity. For the Wounded Warrior, scars not only compromise physical appearance, leading to debilitating aesthetic and psychological effects, but the formation of excessive scar tissue is correlated with restriction in movement (for example, contractures over joints), loss of function, growth restriction, and reduced strength of healed tissue. Normal and hypertrophic scars remain difficult to treat where currently applied therapeutic options remain predominantly symptomatic, empirical, unpredictable, and largely ineffective. The topical silver sulfadiazine (Silvadene®) cream is the standard antimicrobial treatment for burns and skin grafts; however, it does not enhance re-epitheliazation or prevent burn progression. There are no Food and Drug Administration-approved therapeutics that prevent excessive inflammation following burn injury, prevent injury progression, and mitigate scar formation. Current standard of care for severe burn injuries remains early excision and autografting and has not fundamentally changed in over 30 years. FirstString Research has developed a stable, easy-to-use, cutaneous gel (Granexin® gel [Granexin]) containing a small molecule therapeutic (named alphaCT1) that possesses potent anti-inflammatory properties and optimizes the body s injury response mechanism. Treatment of acute burn injuries with Granexin has the potential to improve healing; mitigate scarring; restore skin structure, function, and aesthetics; enhance the integration of skin grafts; and minimize acute complications and chronic functional impairment following acute burn exposure. The proposed Level 1 study will address Fiscal Year 2015 Military Burn Research Program Topic Area 3b by evaluating the efficacy, safety, and therapeutic potential of Granexin in optimizing the healing of acute thermal burn wounds in validated small (mouse) and large (pig) animal full-thickness burn models. The ultimate goal will be to prepare Granexin for clinical testing for indications that include battlefield point-of-care delivery of gels or wound dressings in addition to clinical settings for definitive care to Warfighters with severe burns and other traumatic injuries. Successful completion of this study will provide the needed efficacy data to support the clinical evaluation of Granexin in the treatment of full-thickness burn victims. This study will demonstrate (1) the efficacy of Granexin in attenuating burn extension, expediting healing, and enhancing scarless healing, as compared to routine care in two animal species and (2) the efficacy of Granexin treatment in promoting the integration of skin autografts in a large animal model. Implementation of these studies will allow for stepwise assessment of necessary milestones in the development program, thereby reducing risk. Immediately following completion of the outlined project, FirstString Research will pursue additional Department of Defense funding in order finalize the required toxicity studies to satisfy regulatory requirements for the clinical advancement of Granexin followed by the initiation of clinical trials. Numerous animal toxicity studies in association with four human clinical trials have already confirmed the clinical efficacy and safety of Granexin in enhancing healing outcome when used to treat complex chronic wounds (diabetic foot ulcers and venous leg ulcers). These studies emphasize the limited risks and enormous therapeutic potential associated with incorporation of Granexin into burn treatment protocols. Ulcers treated with Granexin versus control treatments healed significantly faster with a median of 6 weeks compared to 15 weeks, and patients had 74% to 80% incidences
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610716
Entities
People
- Gautam Ghatnekar
Organizations
- FirstString Research (United States)
- United States Army