# Novel pediatric anticonvulsants for nerve agents

> **NIH NIH U01** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 2021 · $746,507

## Abstract

Project Summary
 The main goal of this project is to develop a neurosteroid therapy to mitigate seizures and morbidity caused by
nerve agents and organophosphate (OP) compounds in children and elderly population. Exposure to nerve agents
or OP poisoning can result in persistent seizures, status epilepticus (SE), and severe brain injury. Current
benzodiazepine anticonvulsants do not sufficiently protect from SE, a prolonged seizure activity lasting 30 min or
longer with significant neuronal injury and mortality. Recently neurosteroids have been identified as anticonvulsants
that can effectively control OP seizures and brain injury in adult models. However, the children and elderly are
more vulnerable to nerve agent neurotoxicity, but very few medical countermeasures are available to
protect these populations. This project seeks to address this gap by optimizing a specific anticonvulsant against
nerve agents to stop seizures and prevent brain damage in the pediatric and elderly population. Recent studies
shows that neurosteroids that enhance phasic and extrasynaptic tonic inhibition are strong anticonvulsants against
seizures and brain damage caused by nerve agents. Post-exposure neurosteroid therapy has been shown to be
more effective anticonvulsant and neuroprotective than midazolam in OP intoxication models. The objective of
this project is to determine the efficacy and safety of the synthetic neurosteroid ganaxolone (GX) as ‘broad-
spectrum’ anticonvulsant for nerve agent and OP intoxication in pediatric and aged models. The main
emphasis is focused on IND-enabling efficacy optimization, mechanism, and safety validation of GX in pediatric
rats. The project will address three specific aims: (Aim 1): To determine the efficacy of GX against DFP- and soman-
induced seizures and neuropathology in pediatric rats; (Aim 2): To determine the efficacy of GX against DFP- and
soman-induced seizures and neuropathology in aged rats; and (Aim 3): To determine the pharmacokinetic and
safety profile of GX in pediatric and aged rats and prepare a pre-IND application under the Animal Rule pathway.
The progressive “go/no-go” milestones plan includes quantitative criteria for the success of key studies focusing
on four primary outcome measures: (i) anticonvulsant efficacy; (ii) acute neuroprotectant efficacy; (iii) prevention of
chronic neurodegeneration and neuroinflammation; and (iv) attenuation of epilepsy and long-term neurological
dysfunction. The overall impact of the project’s outcomes will be very high for the development of lifesaving
anticonvulsant drug for OP intoxication in pediatric and elderly population, which is a high priority civilian therapeutic
field for the CounterACT program.

## Key facts

- **NIH application ID:** 10248384
- **Project number:** 5U01NS117209-02
- **Recipient organization:** TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
- **Principal Investigator:** Doodipala Samba Reddy
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $746,507
- **Award type:** 5
- **Project period:** 2020-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10248384

## Citation

> US National Institutes of Health, RePORTER application 10248384, Novel pediatric anticonvulsants for nerve agents (5U01NS117209-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10248384. Licensed CC0.

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