The National Institutes of Health’s National Institute of Environmental Health Sciences has awarded Duke Anesthesiology’s Satya Achanta, PhD, DVM, a two-year $1,109,637 UG3 grant for his project titled, “Identification and Optimization of Medical Countermeasures for Phosgene Inhalation Injuries.”
Phosgene gas is a terrorism and warfare agent and, due to transport and industrial accidents, has injured many Americans. Phosgene targets the lungs, causing severe edema and lung injury after inhalation, with a high fatality rate among those exposed. Despite these devastating effects, no mechanism-based treatment for phosgene injury has been developed.
The renin-angiotensin-aldosterone system (RAAS) plays a key role in cardiopulmonary homeostasis. However, RAAS is dysregulated during acute respiratory distress syndrome (ARDS) contributing to underlying pathophysiology. Pro-resolving mediators that are generated during the inflammation cascade are short-lived due to degradation by an enzyme called soluble epoxide hydrolase (sEH).
Based on Achanta’s preliminary data, he hypothesized that targeting the RAAS and stimulating resolution pathways by administration of soluble epoxide hydrolase inhibitors (sEHIs) post phosgene exposure ameliorates lung injury, leading to decreased morbidity and improved recovery. In the UG3 phase, Achanta and his team will evaluate short-term and long-term therapeutic effects of potential RAAS modulators and sEHIs in rodent models. Upon successful completion of milestones in the UG3 phase, a three-year UH3 phase funding will be granted to evaluate the most effective therapeutic drugs in non-rodent models.
“Successful completion of this research could mark a pivotal advancement in targeted treatments against phosgene gas injuries, addressing a significant gap in current medical countermeasures,” says Achanta, assistant professor in anesthesiology. “Moreover, our work will pave the way for Biomedical Research Development Authority (BARDA)-enabling studies and potentially expedite FDA approval under the Animal Rule, ultimately offering hope for those vulnerable to this deadly chemical.”