# Pediatric model for evaluation of effects of and therapies for high level organophosphate anticholinesterase poisoning.

> **NIH NIH U01** · MISSISSIPPI STATE UNIVERSITY · 2024 · $145,499

## Abstract

Project Summary/Abstract
Many of the organophosphate (OP) anticholinesterases, such as nerve agents, are highly toxic. Terrorist
actions or accidents involving OPs could lead to mass casualties. The current therapy consists of the
muscarinic receptor antagonist atropine and an oxime reactivator of the inhibited acetylcholinesterase (AChE)
(2-PAM in the US). The current testing paradigms to identify improved medical countermeasures are largely
from adult animals, and there is little information available on pediatric therapies. There is some information on
the vulnerability of juvenile animals from the OP insecticide literature, which verifies that the juveniles are more
sensitive to OPs. Thus, there is a need to have a pediatric testing paradigm available to investigate the efficacy
and safety of new countermeasures to OP threats in juvenile animals. We have developed a testing paradigm
in adult rats and have used it for several years to evaluate the efficacy of therapeutic countermeasures in adult
rats using a nerve agent chemistry (nitrophenyl isopropyl methylphosphonate; NIMP, sarin surrogate) and an
OP insecticide chemistry (paraoxon, active metabolite of parathion). The paradigm is particularly relevant to
civilian casualties in that it introduces the antidotes at the time of appearance of signs of poisoning (typically
about 30 minutes) which would be consistent with therapy in the field in a mass casualty situation. We have
developed a platform of novel brain-penetrating oxime AChE reactivators that have shown impressive efficacy
in adult rats; Oxime 20 is our lead candidate. We propose to evaluate this paradigm in juvenile rats (12 and 21
days, 3 and 7 year human equivalent) to verify the natural history of the toxidrome for these 2 OPs (i.e.,
dosage of OP, signs of toxicity, time to severe signs, time to death in lethal dose) (Aim 1a) and the efficacy of
standard of care (atropine + 2-PAM or novel Oxime 20) (Aim 1b). The overarching goal of this supplement is to
develop a pediatric testing paradigm for high dose poisoning by an OP anticholinesterase that will be useful for
the development of new medical countermeasures suitable for infants and children.

## Key facts

- **NIH application ID:** 11083959
- **Project number:** 3U01NS123255-04S1
- **Recipient organization:** MISSISSIPPI STATE UNIVERSITY
- **Principal Investigator:** Janice Elaine Chambers
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $145,499
- **Award type:** 3
- **Project period:** 2021-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11083959

## Citation

> US National Institutes of Health, RePORTER application 11083959, Pediatric model for evaluation of effects of and therapies for high level organophosphate anticholinesterase poisoning. (3U01NS123255-04S1). Retrieved via AI Analytics 2026-06-13 from https://api.ai-analytics.org/grant/nih/11083959. Licensed CC0.

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