Cutaneous Radiation Injuries: Models, Assessment and Treatments

Abstract

Many cases of human exposures to high-dose radiation have been documented, including individuals exposed during the detonation of atomic bombs in Hiroshima and Nagasaki, nuclear power plant disasters (e.g., Chernobyl), as well as industrial and medical accidents. For many of these exposures, injuries to the skin have been present and have played a significant role in the progression of the injuries and survivability from the radiation exposure. There are also instances of radiation-induced skin complications in routine clinical radiotherapy and radiation diagnostic imaging procedures. In response to the threat of a radiological or nuclear mass casualty incident, the U.S. Department of Health and Human Services tasked the National Institute of Allergy and Infectious Diseases (NIAID) with identifying and funding early-to mid-stage medical countermeasure (MCM) development to treat radiation-induced injuries, including those to the skin. To appropriately assess the severity of radiation-induced skin injuries and determine efficacy of different approaches to mitigate/treat them, it is necessary to develop animal models that appropriately simulate what is seen in humans who have been exposed. In addition, it is important to understand the techniques that are used in other clinical indications (e.g., thermal burns, diabetic ulcers, etc.) to accurately assess the extent of skin injury and progression of healing. For these reasons, the NIAID partnered with two other U.S. Government funding and regulatory agencies, the Biomedical Advanced Research and Development Authority (BARDA) and the Food and Drug Administration (FDA), to identify state-of-the-art methods in assessment of skin injuries, explore animal models to better understand radiation-induced cutaneous damage and investigate treatment approaches. A two-day workshop was convened in May 2019 highlighting talks from 28 subject matter experts across five scientific sessions. This report provides an overview of information that was presented and the subsequent guided discussions.

The Ability of the Nitric Oxide Synthases Inhibitor T1023 to Selectively Protect the Non-Malignant Tissues

“…The problem of developing pharmacological agents for the prevention and treatment of RT toxic effects have currently attracted considerable attention. The objects of research and development in this area are an extremely wide range of synthetic and biotechnological compounds with various types of biochemical and pathophysiological activity: the ability to limit the formation of primary radiation damage, modulate the processes of cell death, the activity of post-radiation repair, the course of immune-inflammatory processes and fibrogenesis [20][21][22][23].…”

Cutaneous and local radiation injuries

“…Kerastat completed a clinical trial in 2018 ( NCT03559218 ) and was cleared for a radiation dermatitis indication in 2020. The company continues to advance the product for treatment of CRI/LRI during a radiological or nuclear incident, using a large white pig model [ 133 ].…”

“…In addition to the approaches mentioned above, both BARDA and NIAID have supported contracts for other novel approaches to treat CRI/LRI. These have included investments in TP508 (Chrysalis Biotherapeutics), a thrombin peptide that targets the vasculature to provide mitigation of radiation injuries to the skin [ 143 ], Granexin gel, a product with an active ingredient consisting of the aCT1 peptide, which targets connexin 43 protein, downregulates inflammation, and is in late-stage human trials for a variety of indications (FirstString Research) [ 133 ], and Nor Leu 3-A(1–7) (US Biotest Inc.), an angiotensin analog that has shown promise in accelerating healing of severe radiation-induced lesions [ 122 ].…”

Acute Radiation Syndrome and the Microbiome: Impact and Review

“…Thermal and radiation burns are also likely during a radiation incident. However, standard medical management for thermal burns such as medications, wound dressings, therapy, and surgery may not be appropriate for radiation burns, which have a different damage profile with cyclic waves of inflammation and progressive lesion formation over time ( DiCarlo et al, 2020 ). Adding to this complex scenario is the possibility of bacterial infection.…”