Dystrophin (DMD) pre-messenger RNA exon 51 (DMD exon 51)

The Dystrophin (DMD) pre-mRNA exon 51 splice site region is a therapeutic target for treating Duchenne muscular dystrophy (DMD) in patients with specific frame-shifting mutations. DMD is a severe, progressive muscle-wasting disease caused by the lack of functional dystrophin protein, which is necessary for maintaining muscle fiber stability (Bushby et al., 2010). The target region consists of specific sequences within the pre-mRNA, including splice donor/acceptor sites and exonic splicing enhancers, that are essential for the inclusion of exon 51 in the mature mRNA (Aartsma-Rus et al., 2009). Therapeutic antisense oligonucleotides (ASOs) are designed to bind to this region and sterically block the splicing machinery, leading to the exclusion or "skipping" of exon 51. This exon skipping restores the reading frame of the DMD gene, allowing for the production of a truncated but partially functional dystrophin protein (Mendell et al., 2013). Eteplirsen, a phosphorodiamidate morpholino oligomer, was the first drug approved to target this region to increase dystrophin levels in skeletal muscle (FDA, 2016). Clinical monitoring of this target involves measuring dystrophin protein expression in muscle biopsies and assessing functional improvements through the 6-minute walk test. Despite its success, challenges remain regarding the low efficiency of protein restoration and the difficulty of delivering ASOs to cardiac muscle tissue (Aartsma-Rus et al., 2017).

Other names

DMD exon 51Dystrophin exon 51DMD pre-mRNA exon 51Exon 51 of the DMD gene

Antisense-mediated exon skipping