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
Reengineering a transmembrane protein to treat muscular dystrophy using exon skipping
Quan Q. Gao,Eugene Wyatt,Jeffery A. Goldstein,Peter P. LoPresti,Lisa M. Castillo,Alec Gazda,Natalie Petrossian,Judy U. Earley,Michele Hadhazy,David Y. Barefield,Alexis R. Demonbreun,Carsten G. Bönnemann,Matthew J. Wolf,Elizabeth M. McNally +13 more
TL;DR: The potential for exon skipping has been expanded by testing whether an internal, in-frame truncation of a transmembrane protein γ-sarcoglycan is functional, and an internally truncated Γ-sARCoglycan protein is generated, termed Mini-Gamma by deleting a large portion of the extracellular domain.
Journal ArticleDOI
Making sense of antisense oligonucleotides: A narrative review.
TL;DR: The chemistry, pharmacology, and mechanisms of action of ASOs, preclinical data, and clinical trials in neuromuscular diseases are reviewed and some ethical, regulatory, and policy considerations in the clinical development and use are discussed.
Journal ArticleDOI
Exon Skipping of Hepatic APOB Pre-mRNA With Splice-switching Oligonucleotides Reduces LDL Cholesterol In Vivo
Petra Disterer,Raya Al-Shawi,Stephan Ellmerich,Simon N. Waddington,James S. Owen,J. Paul Simons,Bernard Khoo +6 more
TL;DR: APOB87, like similarly truncated isoforms expressed in patients with a different condition, familial hypobetalipoproteinemia, lowers LDL cholesterol by inhibiting very low-density lipoprotein (VLDL) assembly and increasing LDL clearance, validating APO-skip SSOs as a candidate therapy for FH.
Journal ArticleDOI
Bi-specific splice-switching PMO oligonucleotides conjugated via a single peptide active in a mouse model of Duchenne muscular dystrophy
Fazel Shabanpoor,Graham McClorey,Amer F. Saleh,Peter Järver,Matthew J.A. Wood,Michael J. Gait +5 more
TL;DR: The conjugation of two phosphorodiamidate morpholino oligonucleotide (PMO) SSOs to a single CPP for simultaneous delivery and pre-mRNA targeting of two separate genes, exon 23 of the Dmd gene and exon 5 of the Acvr2b gene, in a mouse model of Duchenne muscular dystrophy is described.
Journal ArticleDOI
Dystrophin rescue by trans -splicing: a strategy for DMD genotypes not eligible for exon skipping approaches
Stéphanie Lorain,Cécile Peccate,Maëva Le Hir,Graziella Griffith,Susanne Philippi,Guillaume Precigout,Kamel Mamchaoui,Arnaud Jollet,Thomas Voit,Luis Garcia +9 more
TL;DR: RNA-based therapeutic approaches using splice-switching oligonucleotides to rescue dystrophin in Duchenne muscular dystrophy preclinical models and are currently being evaluated in DMD patients are applied in vitro, illustrating that a given PTM can be suitable for a variety of mutations.
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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