# Development of a non-opioid chemogenetic therapy for chronic neuropathic pain

> **NIH NIH R43** · CODA BIOTHERAPEUTICS, INC. · 2020 · $497,177

## Abstract

Project Summary/Abstract
Current pharmacological and surgical treatments frequently fail to produce effective and/or durable neuropathic
pain relief and are associated with severe side- or off-target effects. CODA Biotherapeutics is developing a
powerful, targeted approach to treating chronic neuropathic pain that overcomes many conventional limitations.
Our chemogenetic strategy is unique in that it targets the hyperactivity of primary sensory neurons (both
nociceptive and mechanosensitive), a common pathophysiology of neuropathic pain. We have engineered
inhibitory ligand-gated ion channel receptors that lack sensitivity to the endogenous ligand but retain or have
enhanced sensitivity to a clinically safe agonists acquired by CODA (phase 1&2 clinical data packages available).
Localized delivery of the receptor to primary sensory neurons in dorsal root or trigeminal ganglion is readily
achieved using AAV gene therapy combined with standard-of-care procedures. Systemic delivery of the agonist
with oral administration will activate the CODA receptor in a dose-dependent manner. CODA has completed
high-throughput screening of thousands of potential receptor-agonist combinations and has identified several
leads. One current lead, CODA806, when compared to the WT receptor, possesses very high sensitivity to one
of the agonists (Compound-2) and very low sensitivity to its endogenous ligand. In vitro studies in rat DRG
neurons demonstrated that the CODA806 receptor is expressed on the neuronal cell surface, passes chloride
current only with application of Compound-2, and blocks current induced action potentials. These findings have
been extended to show silencing of spontaneous activity in rat DRG and hippocampal cultures. The work
described herein provides a foundation for optimizing the receptor/small-molecule agonist combination and will
demonstrate proof-of-concept in vivo. The first objective is to optimize expression level and durability of
CODA806 in DRG neurons in vivo. We provide AAV pilot data with a GFP reporter molecule showing >50%
transduction of DRG neurons with direct injection. Next, we will conduct proof-of-concept studies of the
CODA806/Compound-2 pair in a rodent model of neuropathic pain (spared-nerve injury). We reduced the risk of
failure and minimized required regulatory safety studies through two strategies (1) CODA has acquired the data
packages for selected agonists and (2) we have selected well established, clinically utilized AAV capsids and
expression cassettes. Therefore, we expect the preclinical\clinical studies will focus on receptor expression and
safety, followed by the safety and efficacy of the receptor\agonist expression (possibly achieved in one clinical
trial). In addition to developing a novel therapy for neuropathic pain, the research described here will further our
understanding of how hyperactivity of sensory neurons (eg, subtypes) plays a role in neuropathic pain and the
potential for novel treatments that m...

## Key facts

- **NIH application ID:** 10157057
- **Project number:** 1R43NS119009-01A1
- **Recipient organization:** CODA BIOTHERAPEUTICS, INC.
- **Principal Investigator:** Annahita Keravala
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $497,177
- **Award type:** 1
- **Project period:** 2020-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10157057

## Citation

> US National Institutes of Health, RePORTER application 10157057, Development of a non-opioid chemogenetic therapy for chronic neuropathic pain (1R43NS119009-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10157057. Licensed CC0.

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