The CounterACT Program is focused on the development of therapeutics and diagnostic tools for chemical threat agents. Research areas supported within this program include the development and validation of in vitro
and animal models for efficacy screening of compounds, efficacy screening of compounds using these models, advanced efficacy and preclinical safety studies with appropriate animal models (including nonhuman primates) using current Good Laboratory Practices (GLP), and clinical studies, including clinical trials with new drugs. The program only supports translational research, defined as the process of applying ideas, insights, and discoveries generated through basic scientific inquiry to the treatment or prevention of human disease. Some examples of preclinical studies the program supports include:
- Creation and development of validated screening assays for therapy development
- Creation and validation of animal models of chemical effects on humans
- Identification of candidate therapeutics using primary or secondary screening efforts
- Development of preliminary proof-of-principle data on the efficacy of candidate therapeutics
- Alternate routes of administration for new or approved therapies that would be safe, effective, and easy to administer during a mass casualty scenario
- Alternate formulations of existing therapeutics that possess physical and chemical characteristics that improve their pharmacokinetics and produce longer shelf lives
Preclinical safety studies, formulation, and current Good Manufacturing Practice (cGMP) synthesis are also supported by the CounterACT program. This is done in part by a contract facility dedicated to this effort. Some more advanced studies the program supports include definitive efficacy studies for U.S. Food and Drug Administration (FDA) approval under the Animal Rule, and Phase I/II clinical trials in humans when appropriate.
Because of the urgency in need and lengthy time and expense in bringing a new compound to regulatory approval, investigators are encouraged to consider drugs that are already approved by the FDA for other indications. Some of these drugs have been shown to be effective in treating victims of chemical exposures, and in some cases, the length of time to regulatory approval for a new indication may be shorter than for a novel compound. CounterACT only supports translational research that is clearly relevant to the development of new or improved therapeutic drugs that will enhance our medical response capabilities during an emergency. New medical countermeasures that have no practical use during a mass casualty situation are not considered. Because many chemical threats have rapid modes of action, the drug should act rapidly to counter these effects. Drugs that are only effective if given prior to chemical insult (pretreatment), or those that must be given within a very short period (1
–15 minutes) after the insult are of lower priority. Drugs that are only effective when administered intravenously are also of low priority, since their use would be impractical in a mass casualty situation. Special emphasis is placed on research relevant to people who are particularly vulnerable, including the young, the elderly, and individuals with pre-existing medical conditions.
There are currently several different classes of therapeutics under study by CounterACT-supported investigators for the various chemical threat agents. These classes include anti-inflammatory compounds, antioxidants, anticholinergic drugs, enzyme reactivators, and others (). Although the toxicities of the various threat agents are exerted by different mechanisms, the ideal medical countermeasure is envisioned to have protective effects against more than one class of chemical threat agent. For example, an anti-inflammatory or antioxidant drug that may be effective in preventing the formation of blisters and lesions due to a cutaneous exposure to a vesicating chemical could, in theory, be efficacious against some of the pulmonary toxicities of an inhalation exposure to a TIC, such as chlorine. Similarly, CounterACT investigators are working on antioxidants and other compounds that show promise as treatments for both chemical and radiation injuries. Broad spectrum activity makes a countermeasure much more attractive for procurement by local and federal health agencies, and possible inclusion in the Strategic National Stockpile.