title: Exon 32 Skipping of Dysferlin Rescues Membrane Repair in Patients' Cells.
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.
authors.affiliation: Aix Marseille Universit é, UMR S 910, Facult é de Médecine de la Timone, Marseille, France.|GMGF, INSERM UMR_ S 910, Marseille, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Barthélémy
authors.affiliation: CNRS UMR 144, 26 rue d'Ulm, Paris Cedex 05, France.|Institut Curie, Centre de Recherche, Laboratoire Trafic, Signalisation et Ciblage Intracellulaires, 26 rue d'Ulm, Paris Cedex 05, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Blouin
authors.affiliation: Aix Marseille Universit é, UMR S 910, Facult é de Médecine de la Timone, Marseille, France.|GMGF, INSERM UMR_ S 910, Marseille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wein
authors.affiliation: INSERM UMR_S 974, Institut de Myologie, Paris, France.|CNRS, UMR7215, Institut de Myologie, Paris, France.|Universit é Pierre et Marie Curie, UM76, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Mouly
authors.affiliation: Aix Marseille Universit é, UMR S 910, Facult é de Médecine de la Timone, Marseille, France.|GMGF, INSERM UMR_ S 910, Marseille, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Courrier
authors.affiliation: Aix Marseille Universit é, UMR S 910, Facult é de Médecine de la Timone, Marseille, France.|GMGF, INSERM UMR_ S 910, Marseille, France.
authors.forename: Eugénie
authors.initials: E
authors.lastname: Dionnet
authors.affiliation: Aix Marseille Universit é, UMR S 910, Facult é de Médecine de la Timone, Marseille, France.|GMGF, INSERM UMR_ S 910, Marseille, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Kergourlay
authors.affiliation: Aix Marseille Universit é, UMR S 910, Facult é de Médecine de la Timone, Marseille, France.|GMGF, INSERM UMR_ S 910, Marseille, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Mathieu
authors.affiliation: INSERM UMR_S 974, Institut de Myologie, Paris, France.|CNRS, UMR7215, Institut de Myologie, Paris, France.|Universit é Versailles-Saint-Quentin, Versailles, France.
authors.forename: Luis
authors.initials: L
authors.lastname: Garcia
authors.affiliation: INSERM UMR_S 974, Institut de Myologie, Paris, France.|CNRS, UMR7215, Institut de Myologie, Paris, France.|Universit é Pierre et Marie Curie, UM76, Paris, France.
authors.forename: Gillian
authors.initials: G
authors.lastname: Butler-Browne
authors.affiliation: CNRS UMR 144, 26 rue d'Ulm, Paris Cedex 05, France.|Institut Curie, Centre de Recherche, Laboratoire Trafic, Signalisation et Ciblage Intracellulaires, 26 rue d'Ulm, Paris Cedex 05, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Lamaze
authors.affiliation: Aix Marseille Universit é, UMR S 910, Facult é de Médecine de la Timone, Marseille, France.|GMGF, INSERM UMR_ S 910, Marseille, France.|AP-HM, Hôpital d'Enfants de la Timone, Département de Génétique Médicale et de Biologie Cellulaire, Marseille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lévy
authors.affiliation: Aix Marseille Universit é, UMR S 910, Facult é de Médecine de la Timone, Marseille, France.|GMGF, INSERM UMR_ S 910, Marseille, France.|AP-HM, Hôpital d'Enfants de la Timone, Département de Génétique Médicale et de Biologie Cellulaire, Marseille, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Krahn
authors.affiliation: Aix Marseille Universit é, UMR S 910, Facult é de Médecine de la Timone, Marseille, France.|GMGF, INSERM UMR_ S 910, Marseille, France.|AP-HM, Hôpital d'Enfants de la Timone, Département de Génétique Médicale et de Biologie Cellulaire, Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Bartoli
keywords: Therapy; dysferlinopathy; exon-skipping; membrane; neuromuscular diseases