# Development of Nav1.7 Monoclonal Antibodies for Treating Pain

> **NIH NIH R43** · INTEGRAL MOLECULAR · 2021 · $474,833

## Abstract

ABSTRACT
Chronic pain is a significant medical problem, affecting over 50 million Americans and representing the largest
cause of disability and disease burden globally. Current pain relief treatments rely heavily on opioid drugs,
which are only partially effective and have a limited therapeutic window. Sustained use of opioids increases the
probability of misuse and addiction, which has led to the current opioid epidemic. Development of efficacious,
non-opioid analgesics could help mitigate this public health crisis and address a significant unmet medical
need. The voltage-gated sodium ion channel Nav1.7 is one of the primary components involved in pain signal
generation. Loss-of-function mutations in the gene encoding Nav1.7 (SCN9A) result in complete insensitivity to
pain in humans. Conversely, gain-of-function mutations contribute to painful peripheral neuropathies. Small
molecule inhibitors of Nav1.7, such as lidocaine, also validate the role of Nav1.7 in pain, but such molecules
cannot be used systemically because they also non-specifically inhibit other sodium channels such as Nav1.5
(required for cardiac function). Despite the remarkable role of Nav1.7 in pain sensation, drugs that specifically
block Nav1.7 have so far proven ineffective in clinical trials. Small molecule therapeutics lack channel subtype
selectivity, and poor bioavailability has made effective dosing difficult in clinical trials. Monoclonal antibodies
(MAbs) offer therapeutic advantages of improved specificity and bioavailability, but there are currently no good
MAbs against Nav1.7. Inhibitory MAbs against ion channels such as Nav1.7 are extremely challenging to
isolate because, unlike soluble proteins, ion channels form complex transmembrane structures, are toxic when
overexpressed, and are difficult to purify away from their native lipid environment. Here we propose to develop
Nav1.7 monoclonal antibodies for treating pain.

## Key facts

- **NIH application ID:** 10318547
- **Project number:** 1R43NS124421-01A1
- **Recipient organization:** INTEGRAL MOLECULAR
- **Principal Investigator:** JOSEPH Benjamin RUCKER
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $474,833
- **Award type:** 1
- **Project period:** 2021-09-20 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10318547

## Citation

> US National Institutes of Health, RePORTER application 10318547, Development of Nav1.7 Monoclonal Antibodies for Treating Pain (1R43NS124421-01A1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10318547. Licensed CC0.

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