Localized Metal Modulation as a First Line Treatment of Burn Injuries

DESCRIPTION (provided by applicant): The proposed Phase I SBIR grant, Livionex Inc. will test and develop a novel approach for the early treatment of burn injuries. Livionex will leverage its knowledge in the use of localized metal modulation, particularly, the control of iron and calcium in the area of the injury, to attenuate the extreme degree of oxidative damage and inflammation that occurs early in the time frame of burn injury progression. Localized metal modulation to down regulate the inflammatory response post burn injuries is a path that has not been tried before. Livionex formulation (LF also designated as ME in our preliminary studies) consists of two GRAS components, a metal chelator and a membrane permeability enhancer. Since we have shown thattopical application of ME crosses membranes and ameliorates ocular and dermal inflammation, a similar approach would work in burn injuries. This is also supported by anecdotal evidence that indicates the topical application of the LF slows the progressionof the burn injury and has also shows early efficacy in a pilot clinical trial to treat inflammatory edema that results from chronic venous insufficiency. Increased amounts of oxidants generated endogenously early on in burns cause increased lipid peroxidation and iron dependent formation of cytotoxic lipid aldehydes, such as 4- hydroxynonenal (HNE) that can induce Ca/Fe-dependent toxic events. More ROS are generated in an autocrine/ paracrine fashion thus amplifying the oxidative and inflammatory damagein a cyclic manner. Thus early down-regulation of inflammation via localized metal modulation soon after the occurrence of the injury will speed healing. Utilizing a rat burn model and Drs Ansari and Herndon's expertise, and facilities at the University of Texas Medical Branch, we propose the following specific aims to show the efficacy of the approach: Specific Aim 1: Evaluate the efficacy of the Livionex formulation in the prevention of dermal full thickness burns (dose response and progression of burn injury over time). Specific Aim 2: Evaluate the effect of the time of treatment initiation after burn injury, on reducing the progression to full thickness burns. Successful completion of the proposed work will give us the grounds to proceed further and ultimately introduce a novel therapeutic strategy against burn injury. Such a topical therapy will have extensive application in hospitals, battle field and may end up being in every first-aid box at home, office and schools, as an early intervention for burn injuries. PUBLIC HEALTH RELEVANCE: Burns are a major cause of accidental death. Injuries from burns can be painful, require many months of treatment, and involve loss of function. Thermal injuries trigger an intense local and systemic inflammatoryresponse. While it is transient systemically, burn wounds suffer from the effects of acute influx of inflammatory mediators and growth factors for an extended time. Burn research and the newest therapies focus on reducing this inflammatory response, intending to limit the progression of burns. Moderate to severe burn injuries requiring hospitalization account for approximately 100,000 of these cases, and about 5,000 patients die each year from burn related complications. Burn injuries incur a significantcost to the health care system in North America and worldwide. In the United States, current annual estimates show that more than US 18 billion is spent on specialized care of patients with major burn injuries. (Church 2006). The Livionex formulation hasthe potential to provide a novel early intervention to burn injuries that is not only safe and effective, but one that also reduces patient hardship and associated health care costs.