Dyne Therapeutics has announced promising preclinical results for DYNE-302, a novel gene therapy targeting facioscapulohumeral muscular dystrophy (FSHD), demonstrating the potential to reverse severe muscle disease in animal models. The company will present these findings at the 32nd Annual FSHD Society's International Research Congress in Amsterdam on June 12-13, 2025.
Functional Recovery in Severe Disease Model
In a mouse model of severe FSHD, a single intravenous dose of DYNE-302 administered at the peak of muscle weakness restored the ability to run on a treadmill. This functional improvement was accompanied by molecular evidence of therapeutic benefit, with analysis of gene activity in skeletal muscle indicating correction of muscle damage and inflammation.
The results suggest that preexisting and severe skeletal muscle disease in FSHD has the potential to be reversed by targeting the DUX4 mRNA with DYNE-302, according to the company's announcement.
Targeting the Root Cause of FSHD
FSHD is a rare, progressive, inherited muscle disease where de-repression of DUX4 in skeletal muscle drives disease pathogenesis, leading to muscle damage and loss of function. This results in symptoms that restrict daily activities and impose high physical, emotional, and financial burdens on patients.
DYNE-302 leverages a TfR1-targeting Fab for muscle delivery of an siRNA payload highly specific for DUX4 mRNA, with the aim of suppressing DUX4 expression and the downstream DUX4 transcriptome. The therapy represents a targeted approach to addressing the underlying molecular mechanism driving FSHD progression.
Significant Unmet Medical Need
An estimated 16,000 to 38,000 individuals in the United States and approximately 35,000 in Europe are affected by FSHD. People living with FSHD experience weakness in all major muscle groups throughout the body and limited mobility, yet there are currently no approved therapies for this condition.
Individuals with FSHD carry a genetic mutation that allows the DUX4 gene to be sporadically activated in muscle cells, causing their gradual destruction throughout the body. The progressive nature of the disease leads to skeletal muscle loss, muscle weakness and wasting across multiple muscle groups.
Expanding Treatment Pipeline
The FSHD therapeutic landscape is evolving, with multiple companies developing novel approaches. According to DelveInsight's assessment, the global FSHD pipeline constitutes more than 10 key companies working toward developing over 10 treatment therapies across various stages of development.
Companies active in FSHD treatment development include Dyne Therapeutics, Avidity Biosciences, Fulcrum Therapeutics, aTyr Pharma, and others. Emerging therapies in different phases of clinical trials include DYNE-301, AOC 1020, Losmapimod, and ATYR 1940, which are expected to have significant impact on the FSHD market in coming years.
Conference Presentation Details
Stefano Zanotti, PhD, Head of Neuromuscular Research at Dyne, will present the oral presentation titled "DYNE-302 leads to functional improvement and resolves muscle transcriptomic changes in mouse models of FSHD" during the Mechanisms of Disease & Interventional Strategies session on Friday, June 13, 2025, at 12:00 p.m. CEST / 6:00 a.m. ET.
The presentation will also be made available in the Scientific Publications & Presentations section of Dyne's website following the session, providing broader access to the research findings for the scientific community.
