# Novel Antibody-Oxime Pairing to Reduce Circulating Organophosphate Levels.

> **NIH NIH U01** · HUMAN BIOMOLECULAR RESEARCH INSTITUTE · 2020 · $605,800

## Abstract

Abstract. This project seeks to investigate new methods that can improve upon the current standard of care
(SOC) used to treat exposures to organophosphate chemicals such as paraoxon (POX). The components of
the SOC in the US are 2-pyridine aldoxime methiodide (2-PAM), atropine and a benzodiazepine (e.g.,
midazolam) that address the reactivation of OP-inhibited acetylcholinesterase, blocks muscarinic receptors from
damaging excitotoxic action from surplus acetylcholine, and acts as an anti-seizure and muscle relaxant.
Although this well-developed cocktail of therapeutic action dramatically improves morbidity and mortality from
OP exposures, the pharmacological action of these therapeutics does not address removal, destruction or
neutralization of the OP in vivo allowing it to circulate freely and continue to act on target and non-target proteins.
This is a serious void in the overall efficacy of the SOC particularly when the OP is long lived in circulation. With
the addition of a strategy or new therapeutic that could remove surplus OP from blood, the SOC would markedly
improve patient outcomes. This application outlines a novel approach in which novel immunotherapeutics will be
devised that bind 2-PAM (from the SOC) as a proxy agent to react with paraoxon and remove it from circulation.
 We will test the hypotheses that catalytic antibodies generated against a transition state representing the
reaction between paraoxon and 2-PAM can be produced and when introduced as part of the SOC accelerates
the breakdown of POX in the bloodstream. We will address the hypotheses by addressing the following specific
aims. SA1. To show that haptens can be designed, synthesized and characterized to generate novel OP-
degrading immunotherapeutics. SA 2. To produce and identify monoclonal antibodies that accelerate the
breakdown of POX using 2-PAM as a proxy nucleophile. SA 3. To determine the ex vivo and in vivo reduction in
POX levels using mAb-oxime pairing as a novel immunotherapeutic.

## Key facts

- **NIH application ID:** 9782548
- **Project number:** 1U01NS112108-01
- **Recipient organization:** HUMAN BIOMOLECULAR RESEARCH INSTITUTE
- **Principal Investigator:** Charles Mark Thompson
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $605,800
- **Award type:** 1
- **Project period:** 2020-05-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9782548

## Citation

> US National Institutes of Health, RePORTER application 9782548, Novel Antibody-Oxime Pairing to Reduce Circulating Organophosphate Levels. (1U01NS112108-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9782548. Licensed CC0.

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