# Preclinical optimization of a gene therapy for erythromelalgia and chronic pain

> **NIH NIH U44** · NAVEGA THERAPEUTICS, INC. · 2021 · $698,171

## Abstract

ABSTRACT
 Chronic pain is pain that persists past the normal time of healing. 1.5 billion people
worldwide suffer from chronic pain and this number continues to increase as the elderly population
grows, the prevalence of diabetes rises, and cancer survival rates improve. Chronic pain not only
severely impacts daily quality of life for many patients, it also places a heavy socioeconomic
burden on society. Due to the limited number of efficacious treatment options available, chronic
pain is often treated with opioids despite the risk of addiction and side effects. Unfortunately, the
prescribing of opioids to treat chronic pain has largely fueled the current opioid epidemic.
Therefore, there is an urgent and clear unmet need for non-addictive alternative analgesics for
the treatment of chronic pain. The push to develop specific and non-addictive alternative
painkillers has brought interest to a particular sodium channel, NaV1.7, shown to be important for
pain sensing. Gain-of-function mutations in NaV1.7 are associated with a disorder characterized
by intense burning pain in the extremities: primary erythromelalgia. Conversely, loss-of function
of NaV1.7 results in the inability to feel pain. Therefore, inhibiting NaV1.7 can be an effective
method of reducing pain and treat erythromelalgia patients. To accomplish this, we designed
epigenetic modulators to repress expression of NaV1.7. Rather than making permanent edits to
the genome, these epigenetic modulators will transiently inhibit expression of NaV1.7. By targeting
NaV1.7 at the DNA-level, we can achieve specific and long-lasting modulation of NaV1.7, with
better pharmacokinetics prospects than RNA- and protein-targeting approaches. In this study, we
propose to optimize these epigenetic modulators as well as their delivery in order to achieve high
specificity and efficacy. In addition, we will evaluate our optimized modulators in small-scale
manufacturing studies as well as toxicological studies in a large animal model. The result of this
study will be an optimized gene therapy that is not only non-addictive and efficacious for treatment
of chronic pain but also highly specific and long-lasting.

## Key facts

- **NIH application ID:** 10220568
- **Project number:** 1U44NS122114-01
- **Recipient organization:** NAVEGA THERAPEUTICS, INC.
- **Principal Investigator:** Fernando Aleman Guillen
- **Activity code:** U44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $698,171
- **Award type:** 1
- **Project period:** 2021-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10220568

## Citation

> US National Institutes of Health, RePORTER application 10220568, Preclinical optimization of a gene therapy for erythromelalgia and chronic pain (1U44NS122114-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10220568. Licensed CC0.

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