Dystrophin gene (DMD) (DMD)

The DMD gene encodes dystrophin, a 427-kDa cytoskeletal protein essential for muscle strength and stability. Mutations in the DMD gene that disrupt the protein's reading frame cause Duchenne muscular dystrophy (DMD), a severe form of muscular dystrophy characterized by progressive muscle weakness, loss of ambulation, cardiomyopathy, and respiratory failure. The most common mutations are deletions spanning one or multiple exons, with two major hotspots: one spanning exons 45-55 and another spanning exons 3-19. Therapeutic approaches for DMD focus on restoring dystrophin expression through various gene-based strategies. Micro-dystrophin gene therapy delivers shortened but functional versions of the dystrophin gene using adeno-associated virus (AAV) vectors. This approach aims to produce a truncated dystrophin protein that retains critical functional domains. Other approaches include exon skipping with antisense oligonucleotides to restore the reading frame, readthrough of nonsense mutations, and CRISPR-based gene editing. Clinical trials have shown promising results, with some patients demonstrating significant expression of micro-dystrophin in muscle fibers and reductions in biomarkers of muscle damage following treatment.

Other names

Duchenne muscular dystrophy geneDystrophin

Micro-dystrophin gene therapy delivers shortened but functional versions of dystrophin via viral vectors. Exon skipping corrects for missing exons in the DMD gene to allow production of more functional dystrophin protein. Read-through of nonsense mutations enables production of full-length protein despite premature stop codons. CRISPR-based gene editing directly modifies the DMD gene.