Functional analysis of MYOD-transduced fibroblasts and urine-derived cells from healthy individual and patients with duchenne muscular dystrophy

Abstract

Background: Duchenne muscular dystrophy (DMD) is a severe muscle disorder characterized by mutations in the DMD gene that mainly disrupt the reading frame, resulting in absence of functional dystrophin. Exon-skipping using short antisense oligonucleotides is a promising therapy for DMD, which aims to convert severe DMD into mild Becker muscular dystrophy by altering pre-mRNA splicing to restore an open reading frame. We employed in vitro assay including myogenic conversion of fibroblasts by MYOD and fluorescence-activated cell sorting (FACS)-aided cell selection, for patient eligibility assessments in a first-in-human exon 53-skipping clinical trial at NCNP. However, a limitation of the in vitro assay is that it requires an invasive skin biopsy. Moreover, detailed characteristics of the MYOD-transduced fibroblasts as myogenic cells are still unclear.