Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study.
Sebahattin Cirak,Virginia Arechavala-Gomeza,Michela Guglieri,Lucy Feng,Silvia Torelli,Karen Anthony,Stephen Abbs,M. E. Garralda,John P. Bourke,Dominic J. Wells,George Dickson,Matthew J.A. Wood,Steve D. Wilton,Volker Straub,Ryszard Kole,Stephen B. Shrewsbury,Caroline Sewry,Jennifer E. Morgan,Kate Bushby,Francesco Muntoni +19 more
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TLDR
The safety and biochemical efficacy presented show the potential of AVI-4658 to become a disease-modifying drug for Duchenne muscular dystrophy.About:
This article is published in The Lancet.The article was published on 2011-08-13 and is currently open access. It has received 847 citations till now. The article focuses on the topics: Duchenne muscular dystrophy & Drisapersen.read more
Citations
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Journal ArticleDOI
Oligonucleotide conjugates for therapeutic applications.
TL;DR: This review gives an overview of current developments of oligonucleotide conjugates for therapeutic applications, including peptides, proteins, carbohydrates, aptamers and small molecules, including cholesterol, tocopherol and folic acid.
Journal ArticleDOI
A Novel Morpholino Oligomer Targeting ISS-N1 Improves Rescue of Severe Spinal Muscular Atrophy Transgenic Mice
Haiyan Zhou,Narinder Janghra,Chalermchai Mitrpant,Rachel L. Dickinson,Karen Anthony,Loren Price,Ian C. Eperon,Stephen D. Wilton,Jennifer E. Morgan,Francesco Muntoni +9 more
TL;DR: PMO25 was the most efficacious in augmenting exon 7 inclusion in vitro in spinal muscular atrophy (SMA) patient fibroblasts and in vitro splicing assays, and naked Morpholino oligomers are more efficient and safer than the Vivo-Morpholino and have potential for future SMA clinical applications.
Journal ArticleDOI
Gene therapy for muscular dystrophy: lessons learned and path forward.
Jerry R. Mendell,Louise R. Rodino-Klapac,Zarife Sahenk,Vinod Malik,Brian K. Kaspar,Christopher M. Walker,K. Reed Clark +6 more
TL;DR: A gene therapy approach using a mini-dystrophin transferred in adeno-associated virus (AAV) and suppression of stop codons to promote readthrough of the DMD gene to increase the size and strength of the muscle is completed.
Journal ArticleDOI
An overview of the clinical application of antisense oligonucleotides for RNA-targeting therapies.
TL;DR: The predominant therapeutic strategies in the antisense field are introduced whilst highlighting recent clinical findings that demonstrate the significant potential of these approaches for development of novel therapies in several diseases.
Journal ArticleDOI
Forelimb Treatment in a Large Cohort of Dystrophic Dogs Supports Delivery of a Recombinant AAV for Exon Skipping in Duchenne Patients
Caroline Le Guiner,Marie Montus,Laurent Servais,Yan Cherel,Virginie François,Jean-Laurent Thibaud,Claire Wary,B. Matot,Thibaut Larcher,Lydie Guigand,Maeva Dutilleul,Claire Domenger,M. Allais,Maud Beuvin,Amélie Moraux,Johanne Le Duff,Marie Devaux,Nicolas Jaulin,Mickaël Guilbaud,Virginie Latournerie,Philippe Veron,Sylvie Boutin,Christian Leborgne,Diana Desgue,Jack-Yves Deschamps,Sophie Moullec,Yves Fromes,Adeline Vulin,Richard H. Smith,Nicolas Laroudie,Frédéric Barnay-Toutain,Christel Rivière,Stephanie Bucher,Thanh-Hoa Le,Nicolas Delaunay,Mehdi Gasmi,Robert M. Kotin,Gisèle Bonne,Oumeya Adjali,Carole Masurier,Jean-Yves Hogrel,Pierre G. Carlier,Philippe Moullier,Philippe Moullier,Thomas Voit +44 more
TL;DR: The concept of a phase 1/2 trial of locoregional delivery into upper limbs of nonambulatory DMD patients is supported, as there was a dose relationship for the amount of exon skipping and histological, nuclear magnetic resonance pathological indices and strength improvement responded in a dose-dependent manner.
References
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Journal ArticleDOI
Dystrophin: The protein product of the duchenne muscular dystrophy locus
TL;DR: The identification of the mdx mouse as an animal model for DMD has important implications with regard to the etiology of the lethal DMD phenotype, and the protein dystrophin is named because of its identification via the isolation of the Duchenne muscular dystrophy locus.
Journal ArticleDOI
Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management
Katharine Bushby,Richard S. Finkel,David J. Birnkrant,Laura E. Case,Paula R. Clemens,Linda H. Cripe,Ajay Kaul,Kathi Kinnett,Craig M. McDonald,Shree Pandya,James Poysky,Frederic Shapiro,Jean Tomezsko,Carolyn M. Constantin +13 more
TL;DR: These recommendations provide a framework for recognising the multisystem primary manifestations and secondary complications of DMD and for providing coordinated multidisciplinary care.
Journal ArticleDOI
Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care
Katharine Bushby,Richard S. Finkel,David J. Birnkrant,Laura E. Case,Paula R. Clemens,Linda H. Cripe,Ajay Kaul,Kathi Kinnett,Craig M. McDonald,Shree Pandya,James Poysky,Frederic Shapiro,Jean Tomezsko,Carolyn M. Constantin +13 more
TL;DR: A comprehensive set of DMD care recommendations for management of rehabilitation, orthopaedic, respiratory, cardiovascular, gastroenterology/nutrition, and pain issues, as well as general surgical and emergency-room precautions are presented.
Journal ArticleDOI
Local Dystrophin Restoration with Antisense Oligonucleotide PRO051
Judith C.T. van Deutekom,Anneke A.M. Janson,Ieke B. Ginjaar,Wendy S. Frankhuizen,Annemieke Aartsma-Rus,Mattie Bremmer-Bout,Johan T. den Dunnen,Klaas Koop,Anneke J. van der Kooi,Nathalie Goemans,Sjef J. de Kimpe,Peter F. Ekhart,Edna H. Venneker,Gerard Johannes Platenburg,Jan J.G.M. Verschuuren,Gert-Jan B. van Ommen +15 more
TL;DR: Intramuscular injection of antisense oligonucleotide PRO051 induced dystrophin synthesis in four patients with Duchenne's muscular dystrophy who had suitable mutations, suggesting that further studies might be feasible.
Journal ArticleDOI
Systemic administration of PRO051 in Duchenne's muscular dystrophy.
Nathalie Goemans,Mar Tulinius,Johanna T van den Akker,Brigitte E Burm,Peter F. Ekhart,Niki Heuvelmans,Tjadine Holling,Anneke A.M. Janson,Gerard Johannes Platenburg,Jessica A. Sipkens,J M Ad Sitsen,Annemieke Aartsma-Rus,Gert-Jan B. van Ommen,Gunnar Buyse,Niklas Darin,Jan J.G.M. Verschuuren,G. Campion,Sjef J. de Kimpe,Judith C.T. van Deutekom +18 more
TL;DR: Systemically administered PRO051 showed dose-dependent molecular efficacy in patients with Duchenne's muscular dystrophy, with a modest improvement in the 6-minute walk test after 12 weeks of extended treatment.
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