# In vivo efficacy studies to support the development of DUX4-targeted RNAi therapy for FSHD

> **NIH NIH R33** · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · 2020 · $388,410

## Abstract

Autosomal dominant facioscapulohumeral muscular dystrophy (FSHD) is among the most prevalent muscular
dystrophies, affecting 1 in 8,333 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
approaches in two novel mouse models of FSHD, 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 a new AAV-
based RNAi therapy for FSHD that can be ultimately used for translation toward our goal of clinical application.

## Key facts

- **NIH application ID:** 9978927
- **Project number:** 5R33NS101166-03
- **Recipient organization:** RESEARCH INST NATIONWIDE CHILDREN'S HOSP
- **Principal Investigator:** Scott Q Harper
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $388,410
- **Award type:** 5
- **Project period:** 2017-08-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978927

## Citation

> US National Institutes of Health, RePORTER application 9978927, In vivo efficacy studies to support the development of DUX4-targeted RNAi therapy for FSHD (5R33NS101166-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9978927. Licensed CC0.

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