Exon skipping to therapeutically restore the frame of an out-of-frame dystrophin mutation has taken center stage in drug development for DMD. The research reviewed here focuses on the clinical development of exon skipping for the treatment of DMD.

The mdx mouse model of Duchenne muscular dystrophy is attributable to a nonsense mutation in exon 23 that blocks translation beyond this point B. Because exon 23 is not a frame-shifting exon, it can be skipped to generate a translatable transcript that produces dystrophin.

Sarepta Therapeutics Announces FDA Approval of AMONDYS 45TM (Casimersen) Injection for the Treatment of Duchenne Muscular Dystrophy (DMD) in Patients Amenable to Skipping Exon 45. Available online: https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-fda-approval-amondys-45tm .

Dec 7, 2024 · The mdx mouse, which harbors a nonsense mutation in exon 23 of Dmd, or genetically engineered mouse models mimicking human DMD mutations, are widely used but have limitations for...

Statistically, exon 51 is the most mutated exon with 14% of the total mutations and 21% of exon deletions, followed by exon 53 with 10% of total mutations and 14% of exon deletions. Point mutations represent around 26% of DMD cases (Happi Mbakam et al. 2022 ).

Antisense-mediated exon-skipping is a promising therapeutic strategy that makes use of synthetic nucleic acids to skip frame-disrupting exon (s) and allows for short but functional protein expression by restoring the reading frame.

Results: Oligonucleotide array analyses with dystrophin pre-mRNA probes revealed strong and highly specific hybridisation patterns spanning the exon 23/intron 23 boundary, indicating an open secondary structure conformation in this region of the RNA.

Multiexon skipping leading to an artificial DMD protein lacking amino acids from exons 45 through 55 could rescue up to 63% of patients with Duchenne muscular dystrophy

May 16, 2018 · Duchenne muscular dystrophy (DMD) is a fatal genetic disorder characterized by progressive muscle wasting that has currently no cure. Exon-skipping strategy represents one of the most promising therapeutic approaches that aim to restore expression of a shorter but functional dystrophin protein.

Feb 17, 2025 · In this study, we evaluated the combination of tricyclo-DNA-ASO targeting the Dmd exon 23 with 20-hydroxyecdysone (20-E), a steroid hormone known to activate the protective arm of the renin-angiotensin-aldosterone system, enhance protein and ATP synthesis, and exhibit anti-inflammatory and antifibrotic properties.