Exon 32 Skipping of Dysferlin Rescues Membrane Repair in Patients' Cells

Overview

Journal J Neuromuscul Dis

Publisher Sage Publications

Specialty Neurology

Date 2016 Nov 19

PMID 27858744

Citations 16

Authors

Florian Barthelemy

Cedric Blouin

Nicolas Wein

Vincent Mouly

Sebastien Courrier

Eugenie Dionnet

Virginie Kergourlay

Yves Mathieu

Luis Garcia

Gillian Butler-Browne

Christophe Lamaze

Nicolas Levy

Martin Krahn

Marc Bartoli

Affiliations

Soon will be listed here.

Abstract

Dysferlinopathies are a family of disabling muscular dystrophies with LGMD2B and Miyoshi myopathy as the main phenotypes. They are associated with molecular defects in DYSF, which encodes dysferlin, a key player in sarcolemmal homeostasis. Previous investigations have suggested that exon skipping may be a promising therapy for a subset of patients with dysferlinopathies. Such an approach aims to rescue functional proteins when targeting modular proteins and specific tissues.We sought to evaluate the dysferlin functional recovery following exon 32 skipping in the cells of affected patients. Exon skipping efficacy was characterized at several levels by use of in vitro myotube formation assays and quantitative membrane repair and recovery tests. Data obtained from these assessments confirmed that dysferlin function is rescued by quasi-dysferlin expression in treated patient cells, supporting the case for a therapeutic antisense-based trial in a subset of dysferlin-deficient patients.

Citing Articles

Expansion of Splice-Switching Therapy with Antisense Oligonucleotides.

Takeshima Y Int J Mol Sci. 2025; 26(5).

PMID: 40076889 PMC: 11899878. DOI: 10.3390/ijms26052270.

Antisense oligonucleotide-mediated exon 27 skipping restores dysferlin function in dysferlinopathy patient-derived muscle cells.

Anwar S, Roshmi R, Woo S, Haque U, Arthur Lee J, Duddy W Mol Ther Nucleic Acids. 2025; 36(1):102443.

PMID: 39967852 PMC: 11834094. DOI: 10.1016/j.omtn.2024.102443.

Analysis of Exon Skipping Applicability for Dysferlinopathies.

Leckie J, Rodriguez S, Krahn M, Yokota T Cells. 2025; 14(3).

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Limb Girdle Muscular Dystrophy Type 2B (LGMD2B): Diagnosis and Therapeutic Possibilities.

Poudel B, Fletcher S, Wilton S, Aung-Htut M Int J Mol Sci. 2024; 25(11).

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The Dysferlinopathies Conundrum: Clinical Spectra, Disease Mechanism and Genetic Approaches for Treatments.

Anwar S, Yokota T Biomolecules. 2024; 14(3).

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