Treating Radiation-Induced Skin Injury and Fibrosis Using Small Molecule Thiol-Modifying Agents
Abstract
Radiation exposure is a pervasive threat to military personnel and civilians alike. The Fukushima disaster illustrates the risks of accidental radiation exposure associated with peaceful use of nuclear energy. In the military realm, the use of ordinance or IEDs (improvised explosive devices) laced with radioactive materials has been identified as a threat. This application focuses on the characterization and development of medical countermeasures to lessen the short- and long-term consequences of skin injuries associated with radiation exposure. It responds to the Fiscal Year 2014 Peer Reviewed Medical Research Program topic area "illnesses related to radiation exposure" and, within this topic area, to acute radiation syndrome (ARS) and delayed effects of acute radiation exposure (DEARE) affecting the skin. In large part, it focuses on the potential of small molecule agents to prevent long-term damage to and functional impairment of connective tissues commonly referred to as "fibrosis." Fibrosis is the hardening of tissues triggered by many events including radiation either alone or in combination with penetrating skin wounds. Dampening the acute inflammation associated with these injuries and boosting wound healing by agents that can be either provided as pills or as topical creams provide an attractive strategy to combat radiation-associated tissue damage and alleviate pain and suffering caused by radiation exposure combined with battlefield injuries. In this proposal, the applicants focus on a class of compounds, which during the last year, has emerged as attractive candidates to treat acute skin damage including damage caused by radiation. The lead agent under investigation has originally been developed to treat inflammation. The prior experience with this and related compounds lends support to the hypothesis that these agents may also have utility in fighting not only radiation-associated acute inflammation but also chronic inflammation and fibrosis. The potential benefits of this and related investigational agents will be investigated in three specific aims focusing on (1) improved healing of acute and long-term radiation-associated skin damage, (2) the benefits of the investigational agents in treating combined injuries caused by radiation and penetrating trauma, and (3) the characterization of mechanisms and molecular changes leading to improved outcomes. At the conclusion of the proposed work, it will be apparent whether further clinical development of these agents for acute and/or delayed radiation injury is warranted. In addition, it is expected that the proposed work will act as a springboard to better understand the mechanisms underlying the benefits of this class of drugs. This will pave the way to further improve the already existing compounds as warranted.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 29, 2016
- Source ID
- W81XWH1510618
Entities
People
- Adam Luginbuhl
Organizations
- Thomas Jefferson University
- United States Army