GDF5 modulation of MuSC pool as a potential therapeutic benefit for DMD
Abstract
Duchenne muscular dystrophy (DMD) is a fatal disease caused by dystrophin deficiency, leading to degeneration of the entire musculature. To improve muscle pathophysiology and gene therapy for DMD, we investigated the potential of growth differentiation factor 5 (GDF5) in the DMD mdx mouse model. We showed that the overexpression of GDF5 in the muscle improved its histology, reduced inflammation, modulated regeneration and induced the appearance of de novo fibers. We demonstrated that muscle satellite cells (MuSCs) are targeted by GDF5 which enhanced their proliferation and slowed down their myogenic commitment and finally their fusion. When combined with AAV-mediated microdystrophin gene therapy, the leading therapeutic strategy, GDF5 further increased the number of microdystrophin-positive fibers compared to gene therapy alone. These findings highlight GDF5 as a promising modulator of DMD pathology and provide the first evidence of a synergistic effect of the combination of GDF5-based intervention and AAV-microdystrophin treatment.
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BibTeX
@article{gentil2026gdf5,
title = {{GDF5 modulation of MuSC pool as a potential therapeutic benefit for DMD}},
author = {Christel Gentil and Aly Bourguiba and Amélie Vergnol and Bruno Cadot and Zoheir Guesmia and Lucile Saillard and Pierre Meunier and Bénédicte Hoareau-Coudert and Mégane Lemaitre and Sestina Falcone and Lorenzo Giordani and France Piétri‐rouxel},
journal = {Molecular Therapy - Nucleic Acids},
year = {2026},
month = oct,
doi = {10.1016/j.omtn.2026.103005},
url = {https://hal.science/hal-05783183v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - GDF5 modulation of MuSC pool as a potential therapeutic benefit for DMD
AU - Christel Gentil
AU - Aly Bourguiba
AU - Amélie Vergnol
AU - Bruno Cadot
AU - Zoheir Guesmia
AU - Lucile Saillard
AU - Pierre Meunier
AU - Bénédicte Hoareau-Coudert
AU - Mégane Lemaitre
AU - Sestina Falcone
AU - Lorenzo Giordani
AU - France Piétri‐rouxel
PY - 2026
DA - 2026/10/07
JO - Molecular Therapy - Nucleic Acids
DO - 10.1016/j.omtn.2026.103005
UR - https://hal.science/hal-05783183v1
AB - Duchenne muscular dystrophy (DMD) is a fatal disease caused by dystrophin deficiency, leading to degeneration of the entire musculature. To improve muscle pathophysiology and gene therapy for DMD, we investigated the potential of growth differentiation factor 5 (GDF5) in the DMD mdx mouse model. We showed that the overexpression of GDF5 in the muscle improved its histology, reduced inflammation, modulated regeneration and induced the appearance of de novo fibers. We demonstrated that muscle satellite cells (MuSCs) are targeted by GDF5 which enhanced their proliferation and slowed down their myogenic commitment and finally their fusion. When combined with AAV-mediated microdystrophin gene therapy, the leading therapeutic strategy, GDF5 further increased the number of microdystrophin-positive fibers compared to gene therapy alone. These findings highlight GDF5 as a promising modulator of DMD pathology and provide the first evidence of a synergistic effect of the combination of GDF5-based intervention and AAV-microdystrophin treatment.
SN - 2162-2531
ER -