Experimental therapies for Duchenne muscular dystrophy

Overview of current and proposed experimental therapies for Duchenne muscular dystrophy (DMD).

(A) AAV-mediated gene therapy employs viral vectors to deliver micro- or mini-dystrophin genes. Clinical trials using different AAV serotypes have shown promise for the treatment of patients with DMD.

(B) Exon-skipping strategies seek to mask exons adjacent to others that have been deleted. This results in the restoration of the reading frame and permits the translation of a slightly smaller dystrophin product.

(C) Stop codon read-through is a small molecule therapy aimed at reducing ribosomal sensitivity to mRNA stop codons, thus promoting ongoing dystrophin translation in those patients with nonsense mutations.

(D) Genome editing, employing a CRISPR/Cas9 platform, has the potential to target specific pathogenic variants in the DMD gene but carries a risk of off-target effects.

AAV: adeno-associated virus; ABD: acting binding domain; AON: antisense oligonucleotide; CR: cystein-rich domain; CRISPR: clustered regularly interspaced short palindromic repeats; mRNA: messenger RNA; PTC: premature termination codon; sgRNA: single guide RNA.

From: Bez Batti Angulski A, Hosny N, Cohen H, et al. Duchenne muscular dystrophy: disease mechanism and therapeutic strategies. Front Physiol 2023; 14:1183101. Copyright © 2023 The Authors. https://www.frontiersin.org/articles/10.3389/fphys.2023.1183101 (Accessed on December 19, 2023). Reproduced under the terms of the Creative Commons Attribution License 4.0.

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Experimental therapies for Duchenne muscular dystrophy