Golodirsen restores DMD transcript imbalance in Duchenne Muscular Dystrophy patient muscle cells.

ABSTRACT:

Background

Antisense oligonucleotides (AON) represent a promising treatment for Duchenne muscular dystrophy (DMD) carrying out-of-frame deletions, but also show limitations. In a completed clinical trial golodirsen, approved by FDA to induce skipping of DMD gene exon 53 in eligible patients, we demonstrated increase in DMD expression and protein production, albeit with inter-patient variability.

Methods

Here, we investigate further the golodirsen mechanism of action using myotubes derived from MyoD transfected fibroblasts isolated from DMD patients at the baseline of the clinical trial SRP-4053.

Results

We confirm golodirsen's selectivity and efficiency in removing only exon 53. For the first time in human cells, we revealed a significant reduction in the so called DM

SUBMITTER: Rossi R 

PROVIDER: S-EPMC11606086 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature