Duchenne muscular dystrophy: organoids used to investigate the limitations of gene therapy
Tested in three-dimensional muscle structures mimicking Duchenne muscular dystrophy, gene therapy improved muscle function without reducing the fibrosis characteristic of the disease.
In Duchenne muscular dystrophy, caused by the absence of dystrophin, the efficacy of gene therapy remains limited despite positive results in animal models. To better understand this partial efficacy and identify more effective therapeutic strategies, French researchers supported by AFM-Téléthon developed muscle organoids called “MYOrganoids”.
Organoids are three-dimensional structures derived from human stem cells (iPS cells) that reproduce the tissue and molecular complexity of an organ in order to better understand its development. When generated from disease-specific iPS cells, they can be used to study pathological mechanisms and test potential therapies.
Organoids reproducing diseased muscle
“MYOrganoids” are generated from iPS-derived muscle cells and fibroblasts (connective tissue cells involved in muscle structure), making it possible to reproduce both the muscle weakness and fibrosis characteristic of Duchenne muscular dystrophy.
Gene therapy delivering the gene encoding a microdystrophin using a viral vector was tested in these MYOrganoids. It improved muscle function but had only limited effects on fibrosis, which persisted. These findings suggest that concomitant antifibrotic treatment could improve the efficacy of gene therapy.
Source
Disease exacerbation in human DMD MYOrganoids enables gene therapy evaluation and unveils persistence of fibrotic activity
Palmieri L, Bimbi G, Ferrand M et al.
NPJ Regen Med. 2026 Jan.