Hemoglobin, Heme, and Iron Scavenging for Improved Burn Injury Outcomes

Project Details

Description

After burn injury to the skin, while some of the skin is irreversibly damaged, there is a region of tissue around the initial burn that is still alive but undergoes extensive inflammation. While this inflammation is part of the normal response of the body to the trauma, in cases of severe injuries, excessive inflammation can cause this tissue to die, which results in an expansion of the original burn-related tissue damage, both in area and depth. This process occurs over the next 24 to 48 hours following the initial injury. Thus, there is an opportunity to intervene so that expansion of the burn is prevented. By limiting the tissue damage, the wound healing process will be faster and scarring that results from the burn healing will be less severe.

Damage to the blood vessels in the burn wound causes the release of hemoglobin from red blood cells. Once outside of red blood cells, hemoglobin easily loses its iron. Free iron potentiates the deleterious impact of inflammation by promoting oxidative damage to cells and tissues. In this project, we develop a cocktail of proteins isolated from blood that can scavenge and remove these sources of free iron and, as a result, decrease cell and tissue damage that ensues after burn injury. Free iron also promotes bacterial growth, and an additional benefit of this therapy is that by removing iron, the risk of bacterial infection may be decreased.

The FY19/20 MBRP IDA Focus Area that is addressed in this proposal is novel therapeutic interventions to prevent burn wound conversion, where 'conversion' refers to the process whereby delayed tissue damage occurs around the burn, thus resulting in a larger, deeper injury than that caused by the initial burn.

We envision that soldiers who suffer from burns could be treated with this product at the site of injury occurrence or immediately upon evacuation to a safer location. Other aspects of burn care would not be changed, but the expectation is that doctors will have smaller injuries to address in patients who have been treated with this product.

The proposed studies will test the clinical efficacy of this product in a relevant animal model of burn injury. If successful, the data would provide evidence to support future human trials. The product would benefit human patients by limiting long-term complications from burn injury healing. The use of blood-related products involves a risk of disease transmission to patients; however, this is a well-known risk that is managed using extremely well-established regulatory procedures in place for other blood-derived products (such as red blood cells, plasma, platelets, etc.) currently used in medicine.

Our experimental plan is designed to determine the route of administration and dosage of the product to achieve a clinically relevant outcome in an animal model of skin burns. The next step after this 3-year research program would be to secure funding to support clinical studies in humans.

StatusActive
Effective start/end date1/1/19 → …

Funding

  • Congressionally Directed Medical Research Programs: $500,000.00

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