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. 2017 Sep 12;136(11):979-981.
doi: 10.1161/CIRCULATIONAHA.117.028382.

Mutation-Based Therapy for Duchenne Muscular Dystrophy: Antisense Treatment Arrives in the Clinic

Elizabeth M McNally  1 , Eugene J Wyatt  2
Affiliations

Mutation-Based Therapy for Duchenne Muscular Dystrophy: Antisense Treatment Arrives in the Clinic

Elizabeth M McNally et al. Circulation. .
No abstract available

Keywords: exons; genetics.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interests Disclosure

EMM and EW are co-inventors of a patent related to exon skipping.

Figures

Figure
Figure
Eteplirsen (Exondys51) mediated readframe correction of DMD mutations. A. Top row: schematic of the dystrophin protein and its domains. ABD1, actin binding domain; H, hinge regions; CR, cysteine rich domain; CT, C-terminal domain; Numbered are the spectrin-like repeats. Red bar, indicates the approximate exon 51 targeting region. Middle rows: Schematic showing eteplirsen-mediated reading frame correction of a DMD frameshift mutation. The normal dystrophin locus from exons 41 to 52 is shown indicating the reading frame of each exon. Many DMD patients have variable sized deletions spanning exons 47 to 50, disrupting the reading frame (dashed blue line). Eteplirsen (red box) is an antisense oligonucleotide that binds to exon splicing enhancer sequences in exon 51 causing its exclusion from mRNA. By excluding 51, exons 46 (or 47, 48 and 49) joins to exon 52 (solid blue line) to restore an open reading frame. B. Antisense oligonucleotides have complementary sequences to those within an exon, in this case Exon 51. Chemical modifications to the antisense oligonucleotides permit the double stranded hybrid to evade nucleases that would normally target the hybrid for destruction. C. Two antisense chemical modifications are shown that were tested as drugs for treating DMD. The first, 2’-O-methyl-phosphorothioate (2’OE Me) is a charged moiety that was tested in drisapersen. The second, phophorodiamidate morpholino (PMO) was used in eteplirsen.
See this image and copyright information in PMC

References

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