# Treatment of Chemotherapy-Induced Peripheral Neuropathy via Genetic Repression of Sodium Channels

> **NIH NIH R44** · NAVEGA THERAPEUTICS, INC. · 2022 · $1,283,183

## Abstract

Project Summary/Abstract
The goal of this project is to develop a gene therapy product that relieves chemotherapy-induced peripheral
neuropathy (CIPN) in a non-permanent, non-addictive and long-lasting manner to improve the quality of
life of cancer patients. Current management of CIPN and cancer pain is very poor, with 1 in 3 patients not
receiving pain medication considered appropriate for the intensity of pain experienced. With the limited
efficacious treatment options available, opioids are often prescribed, however these can lead to addiction.
We are in urgent need of novel pain therapies that would alleviate the side effects of opioids. Voltage-
gated sodium channels (NaV family) have been used in nociceptive transmission and contribution to the
hyperexcitability in primary afferent nociceptive neurons. Additionally, many chemotherapy agents induce
ion channel expression including NaV1.7 and NaV1.8, leading to CIPN. Hence, these sodium channels
have been attractive targets for developing chronic pain therapies. However, the high homology of human
NaV proteins has frustrated most efforts to develop selective protein inhibitors. Instead of targeting the
protein, Navega proposes to develop a non-permanent epigenome regulation tool to target pain. This
novel approach is non-addictive, highly specific, and long-lasting. During Phase I, we determined that the
simultaneous inhibition of NaV1.7 and NaV1.8, was more efficacious at reversing CIPN than repressing
each channel alone. We also demonstrated the safety of our approach at doses tested in mice. During
Phase II we will: 1) perform dose-range studies in mice to determine the therapeutic window; 2) optimize
our reagents to target the human genome; and 3) perform GLP definitive safety studies in NHPs. We will
prepare an IND application to the FDA, and will submit it at the end of the Phase II project. Our final goal
is to develop novel therapeutics that can mitigate CIPN through the use of a specific gene therapy approach
that can simultaneously target two voltage gated sodium channels (something not possible with small
molecules) and provide an alternative treatment to opioids for patients with chronic pain.

## Key facts

- **NIH application ID:** 10487589
- **Project number:** 5R44CA239940-03
- **Recipient organization:** NAVEGA THERAPEUTICS, INC.
- **Principal Investigator:** Fernando Aleman Guillen
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,283,183
- **Award type:** 5
- **Project period:** 2019-09-10 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10487589

## Citation

> US National Institutes of Health, RePORTER application 10487589, Treatment of Chemotherapy-Induced Peripheral Neuropathy via Genetic Repression of Sodium Channels (5R44CA239940-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10487589. Licensed CC0.

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