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

Florian Barthelemy 1 Cedric Blouin 2 Nicolas Wein 1 Vincent Mouly 3 Sebastien Courrier 1 Eugenie Dionnet 1 Virginie Kergourlay 1 Yves Mathieu 1 Luis Garcia 4 Gillian Butler-Browne 5 Christophe Lamaze 2 Nicolas Lévy 6 Martin Krahn 1 Marc Bartoli 1
1 GMGF - Génétique Médicale et Génomique Fonctionnelle
2 CDC - Compartimentation et dynamique cellulaires
3 Centre de recherche en myologie
4 UVSQ Santé - UVSQ - UFR des sciences de la santé Simone Veil
5 Institut de Myologie
6 Département de génétique médicale [Hôpital de la Timone - APHM]
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.
Keywords : Therapy membrane neuromuscular diseases dysferlinopathy exon-skipping
Type de document :
Article dans une revue
Journal of Neuromuscular Diseases, IOS Press, 2015, 2 (3), pp.281-290. 〈10.3233/JND-150109〉
Liste complète des métadonnées

Littérature citée [45 références]  Voir  Masquer  Télécharger
https://hal-amu.archives-ouvertes.fr/hal-01662831
Contributeur : Marc Bartoli <>
Soumis le : mercredi 13 décembre 2017 - 14:42:59
Dernière modification le : mercredi 4 avril 2018 - 11:14:01

Fichier

Exon 32 Skipping of Dysferlin ...
Fichiers produits par l'(les) auteur(s)

Identifiants

Collections

UNIV-AMU | UPMC | CURIE | UVSQ | CEA | FNCLCC | PSL | U974 | UMR144 | MMG | UNIV-PARIS-SACLAY

Citation

Florian Barthelemy, Cedric Blouin, Nicolas Wein, Vincent Mouly, Sebastien Courrier, et al.. Exon 32 Skipping of Dysferlin Rescues Membrane Repair in Patients' Cells. Journal of Neuromuscular Diseases, IOS Press, 2015, 2 (3), pp.281-290. 〈10.3233/JND-150109〉. 〈hal-01662831〉

Exporter

BibTeX TEI DC DCterms EndNote

Partager

Métriques

Consultations de la notice

159

Téléchargements de fichiers

26

Contact

support.ccsd.cnrs.fr
hal.support@ccsd.cnrs.fr
Logo CCSD