Dystrophin pre-messenger RNA exon 44 (DMD exon 44)

The Dystrophin (DMD) pre-messenger RNA exon 44 region is a critical therapeutic target for the treatment of Duchenne muscular dystrophy (DMD) in patients with specific frame-shifting mutations [Aartsma-Rus et al., 2017]. DMD is a progressive neuromuscular disorder caused by the absence of functional dystrophin protein, which is essential for maintaining the structural integrity of muscle fibers [UniProt P11532]. By utilizing antisense oligonucleotides (ASOs) that hybridize to the exon 44 region, the splicing machinery can be directed to bypass this exon during mRNA processing [FDA, 2020]. This exon skipping strategy restores the reading frame, enabling the production of a truncated but partially functional dystrophin protein, similar to that found in the milder Becker muscular dystrophy [Clemens et al., 2020]. Drugs such as viltolarsen are specifically designed to target this region to improve motor function and slow disease progression in amenable patients [Komaki et al., 2020]. The therapeutic goal is to increase the levels of dystrophin in skeletal muscle, thereby reducing muscle damage and inflammation [Heo, 2020]. This target is specifically relevant for approximately 6-8% of DMD patients whose mutations are amenable to exon 44 skipping [Bladen et al., 2015]. Clinical monitoring of this target involves assessing the percentage of dystrophin-positive fibers and overall protein levels via muscle biopsy [Clemens et al., 2020].

Other names

DMD pre-mRNA exon 44Dystrophin exon 44DMD exon 44 regionDystrophin (DMD) pre-mRNA exon 44

Antisense oligonucleotide-mediated exon skipping to restore the mRNA reading frame