Progress and Challenges in Developing Medical Countermeasures for Chemical, Biological, Radiological, and Nuclear Threat Agents

This Commentary delves into the current progress and chal-lenges on ongoing research on medical countermeasures (MCs) for chemical, biologic, radiologic, and nuclear (CBRN) threats. CBRN agents pose a serious risk to human health and safety, with the potential for mass casualties in both military and civilian settings. Chemical threats are toxic compounds that could be used in a terrorist attack, an accidental release, or chemical war-fare. They include nerve agents, organophosphates, pulmonary agents, metabolic/cellular agents, vesicants, ocular toxicants, and opioid agents. Developing effective MCs is crucial for miti-gating the acute and chronic effects of exposure to CBRN agents. The papers in this special issue of JPET highlights the latest advancements in MC research, showcasing insightful out-comes on experimental models, mechanisms, and translational research on MCs for CBRN threats. They portray several notable contributions, including the development of neurosteroid and combination anticonvulsant therapies for nerve agent poisoning, the exploration of chronic impacts and diagnostic tracers for OP neurotoxicity, the establishment of innovative pediatric OP models, the identification of novel molecules for ocular, pulmonary and vesicant injuries, and the repurposing of existing drugs for the treatment of botulism, cyanide, and OP poisoning. These crucial outcomes underscore the breadth of current research covering a variety of chemical threats. Overall, this collection of articles highlights the importance of ongoing research and development in the field of MCs, emphasizing the potential of these counter-measures to effectively treat and mitigate the effects of toxicant exposures and thereby enhance our preparedness for mass ca-sualty incidents. SIGNIFICANCE STATEMENT CBRN agents pose a significant threat to public health. Effec-tive MCs exist for certain chemical threats, but there is a need for new and improved MCs for many others. The research pre-sented in this special issue of JPET highlights the latest ad-vancements in MCs for CBRN threats. This research has the potential to lead to the development of new and repurposed MCs that are more effective, broad-spectrum, and easier to admin-ister to mitigate acute and long-term consequences of chemical exposures.