# Project 2: DUX4 inhibition with non-coding RNAs as a therapeutic strategy for facioscapulohumeral muscular dystrophy (FSHD)

> **NIH NIH P50** · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · 2020 · $282,063

## Abstract

Project Summary/Abstract 
Autosomal dominant Facioscapulohumeral muscular dystrophy (FSHD) is among the most prevalent muscular 
dystrophies, affecting 1 in 7,500 to 1 in 20,000 individuals. FSHD was formally classified as a major form of 
muscular dystrophy in 1954, but the pathogenic events leading to the disease have only recently started 
coming into focus. Several studies now support an FSHD pathogenesis model involving aberrant expression of 
the DUX4 gene, which encodes a myotoxic transcription factor. The emergence of DUX4 represented a 
momentum shift in the FSHD field as it provided an important target for therapy design. Indeed, as FSHD is 
currently untreatable, developing effective FSHD therapies is a critical need in the field. We hypothesized that 
an FSHD treatment should center on inhibiting toxic DUX4 expression in skeletal muscles. The objective of this 
proposal is to develop safe and effective prospective FSHD therapies aimed at reducing toxic DUX4 with RNAi 
and antisense exon skipping approaches in mouse muscles, using therapeutic non-coding RNAs delivered by 
adeno-associated viral vectors (AAV). We have designed three Specific Aims to accomplish this objective. 
Upon completion of these Aims, we expect to produce pre-clinical data supporting the translation of new AAV- 
based RNAi and antisense therapies for FSHD that can be ultimately used for translation toward our goal of 
clinical application.

## Key facts

- **NIH application ID:** 10017026
- **Project number:** 5P50AR070604-05
- **Recipient organization:** RESEARCH INST NATIONWIDE CHILDREN'S HOSP
- **Principal Investigator:** Scott Q Harper
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $282,063
- **Award type:** 5
- **Project period:** 2016-09-14 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017026

## Citation

> US National Institutes of Health, RePORTER application 10017026, Project 2: DUX4 inhibition with non-coding RNAs as a therapeutic strategy for facioscapulohumeral muscular dystrophy (FSHD) (5P50AR070604-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10017026. Licensed CC0.

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