# Soman-induced neuropathology in Gottingen minipig: large animal model assessment for MCM

> **NIH NIH R21** · GENEVA FOUNDATION · 2020 · $153,964

## Abstract

It is important to comprehensively characterize the natural history of chemical warfare nerve agent (CWNA)
toxicity in animal models that represent the human condition so that the FDA Animal Rule may be used to develop
effective medical countermeasures (MCM) against chemicals that cannot be assessed in humans. Currently
there are no approved MCM to treat status epilepticus (SE) that is refractory to benzodiazepine therapy when
treatment is delayed after CWNA exposure or the long-term functional and neuropathological effects of CWNA
exposure. Minipigs, which are similar in anatomy and physiology to humans, are increasingly being used as
large animal alternatives to nonhuman primates. The goal is to develop, characterize and qualify the Gottingen
minipig as a large animal for MCM development to predict effects in humans. A few studies have been conducted
using the minipig to assess lethality and cardiotoxicity of CWNA exposure (e.g. Hulet et al., 2014) and to assess
the efficacy of MCM in increasing survival against CWNA (Saxena, 2011, 2015), the potential for the minipig to
be used as a large animal model to assess seizure-induced brain pathology after exposure to CWNA and to
evaluate MCM has not been assessed. A recent study used the Gottingen minipig as an experimental model to
show neuronal loss following multiple blasts including loss of neurons in the hippocampus and
neuroinflammatory responses including astrocyte activation and activated microglia (Goodrich et al., 2016). Our
specific aim is determine if the Gottingen minipig will be a useful model to evaluate neuroprotective effects of
MCM against CWNA exposure. We propose to first establish the LD50 for intramuscular exposure to soman and
to then evaluate standard MCM of atropine against a lethal challenge dose of soman in minipigs to include
delayed treatment with benzodiazepine. Neuropathological effects of soman exposure in minipigs to include
neuronal loss and neuroinflammation will be evaluated to determine if this model may be useful as a large animal
model for screening FDA-approved anti-epileptic drugs and novel neuroprotectants against soman toxicity. If
validated, this model could then be used in future studies to evaluate MCM against CWNA in support of the FDA
Animal Rule.

## Key facts

- **NIH application ID:** 9921503
- **Project number:** 5R21NS110556-02
- **Recipient organization:** GENEVA FOUNDATION
- **Principal Investigator:** Lucille Lange
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $153,964
- **Award type:** 5
- **Project period:** 2019-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9921503

## Citation

> US National Institutes of Health, RePORTER application 9921503, Soman-induced neuropathology in Gottingen minipig: large animal model assessment for MCM (5R21NS110556-02). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/9921503. Licensed CC0.

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