# An iPSC-Derived NRSF-Dependent Epigenetic Model of Neuropathic Pain

> **NIH NIH R21** · MICHIGAN STATE UNIVERSITY · 2020 · $430,375

## Abstract

PROJECT SUMMARY
It is also becoming clear that many diseases have an epigenetic component. However, in neurological diseases,
such as neuropathic pain, it has been shown that certain genes for ion channels and pain receptors are
downregulated and maintained through epigenetic silencing. Current treatments for neuropathic pain use pain
killers which provide temporary relief for patients, but fail to cure damaged nerves. Further, the long-term use of
pain killers carry a high risk of addiction. Thus, better approaches to treat neuropathic pain are urgently needed.
Studies have linked changes in genes involve in neuropathic pain to the master transcriptional repressor, neuron-
restrictive silencing factor (NRSF). NRSF silences gene expression by recruiting chromatin modifiers to leave
repressive epigenetic marks including histone deacetylases, histone methytransferases, and DNA
methytransferases, on neural genes involved in neuropathic pain. NRSF has been investigated as a therapeutic
target and efforts to modulate its activity through small molecules, siRNA, and mimetics have been attempted.
Since the transcriptionally repressive function of NRSF is mediated through epigenetic mechanisms, we propose
that a Cas9-based approach to actively reverse repressive epigenetic marks left by NRSF on ion channel and
pain receptor genes could provide a novel therapeutic strategy for treating neuropathic pain. This provides
advantages over approaches using pan-acting small molecules and mimetics because it (1) would enzymatically
remove and replace epigenetic marks, and (2) can be targeted to genes of interest in a sequence specific
manner. To achieve these goals, first, we propose to develop an in vitro cell-based model of neuropathic pain
dependent on NRSF-mediated repression, and secondly, we will explore a Cas9-based approach to reverse the
repressive epigenetic marks brought about by NRSF on genes involved in neuropathic pain. This project will
highlight epigenetic marks themselves as possible therapeutic targets and show that a Cas9-based system could
be used therapeutically with a high degree of specificity.

## Key facts

- **NIH application ID:** 9956262
- **Project number:** 1R21NS116496-01
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** CHRISTINA CHAN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $430,375
- **Award type:** 1
- **Project period:** 2020-04-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9956262

## Citation

> US National Institutes of Health, RePORTER application 9956262, An iPSC-Derived NRSF-Dependent Epigenetic Model of Neuropathic Pain (1R21NS116496-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/9956262. Licensed CC0.

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