Examples of Threat Agents
- Cholinergics and convulsant agents that cause seizures and neuropathology
- Cellular respiration inhibitors and other agents that target the blood
- Agents that target the lower and/or upper pulmonary/respiratory tract and may cause pulmonary edema
- Vesicating agents that cause skin and/or ocular pathologies
Categories of research supported under this program include, but are not limited to:
- Mechanistic research strictly to identify translatable targets for therapeutic development and/or intervention, e.g., research on the molecular mechanisms of toxicity for the purpose of identifying novel biomarkers and/or drug targets
- Creation of animal models with response predictive for humans to evaluate lethality and serious near- and long-term sublethal morbidities caused by chemical threats after an acute insult that can be extrapolated to various subpopulation groups (e.g., pediatric, pregnant), i.e., natural history of the condition, time course of progression, and manifestation of the injuries to identify the trigger for intervention. The intended use of the model must be to validate the development of therapeutics.
- Detailed understanding of the pathophysiological mechanism of toxicity of the threat chemical based on dose, quantification of exposure, individual variability in susceptibility and response.
- Development of preliminary in vivo proof-of-principle data on the efficacy of candidate therapeutics, e.g., defining the exact mechanism of action of the lead candidate therapy to prevent or substantially reduces the toxic effects of the chemical threat and relate this from the animal model to humans. This may include assessing in vitro activities (e.g., affinity, specificity, activity in cells, cellular uptake)
Special consideration will be given to research relevant to people who are particularly vulnerable, including pregnant women, infants, the young, the elderly, and individuals with pre-existing medical conditions. Animal models and studies that address these vulnerabilities as well as long term effects after an acute exposure event are of interest. An animal model is defined as a specific combination of an animal species, challenge agent, and route of exposure that produces a disease process or pathological condition that in multiple important aspects corresponds to the human disease or condition of interest.
- How to Write NIH CounterACT Milestones
- NIH CounterACT FAQs
- HHS Definition of Technology Readiness Levels (TRL) of Medical Countermeasures for Chemical Threats
When using these criteria, a medical countermeasure product should be rated at a particular level only after the sponsor has completed all activities listed in that level (e.g., a product is rated at TRL 4 once it completes all of the activities listed in TRL 4)
- U.S. National Library of Medicine's TOXNET