Disease exacerbation in human DMD MYOrganoids enables gene therapy evaluation and unveils persistence of fibrotic activity.

ABSTRACT: Leading gene therapy approaches for Duchenne muscular dystrophy (DMD) using AAV-mediated delivery of microdystrophin (µDys) have shown partial efficacy in patients, contrasting with the favorable outcomes observed in animal models. The identification of effective therapeutic strategies could be accelerated by using human high-throughput DMD models that replicate the molecular complexity driving pathology for accurate screening. To face this challenge, we develop MYOrganoids, an engineered muscle platform derived from patient-induced pluripotent stem cells (iPSC), recapitulating critical hallmarks of DMD, such as fibrosis and muscle dysfunction. We show that co-culture of fibroblasts with iPSC-derived muscle cells during organoid generation is pivotal for functional maturation and muscle fo

SUBMITTER: Palmieri L 

PROVIDER: S-EPMC12820250 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature