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
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Patent
Antisense nucleic acids
TL;DR: In this paper, an oligomer which efficiently enables to cause skipping of the 53rd exon in the human dystrophin gene was presented. And a pharmaceutical composition which caused skipping of this exon with high efficiency.
Journal ArticleDOI
Efficacy and Safety Profile of Tricyclo-DNA Antisense Oligonucleotides in Duchenne Muscular Dystrophy Mouse Model
Karima Relizani,Graziella Griffith,Lucia Echevarria,Faouzi Zarrouki,Patricia Facchinetti,Cyrille Vaillend,Christian J. Leumann,Luis Garcia,Aurélie Goyenvalle +8 more
TL;DR: It is shown that systemic delivery of 13-mer tcDNA allows restoration of dystrophin in skeletal muscles and to a lower extent in the brain, leading to muscle function improvement and correction of behavioral features linked to the emotional/cognitive deficiency.
Journal ArticleDOI
Preventing formation of toxic N-terminal huntingtin fragments through antisense oligonucleotide-mediated protein modification.
Melvin M. Evers,Hoang-Dai Tran,Ioannis Zalachoras,Onno C. Meijer,Johan T. den Dunnen,Gert-Jan B. van Ommen,Annemieke Aartsma-Rus,Willeke M. C. van Roon-Mom +7 more
TL;DR: The proof of concept shows a completely novel approach to reduce mutant huntingtin toxicity not by reducing its expressing levels, but by modifying the huntingtin protein.
Journal ArticleDOI
Innate Immune Response and Off-Target Mis-splicing Are Common Morpholino-Induced Side Effects in Xenopus.
George E. Gentsch,Thomas Spruce,Rita S. Monteiro,Nick D.L. Owens,Stephen R. Martin,James C. Smith +5 more
TL;DR: It is concluded that while MOs can be useful to profile loss-of-function phenotypes at a molecular level, careful attention must be paid to their immunogenic and off-target side effects.
Journal ArticleDOI
A dystrophic Duchenne mouse model for testing human antisense oligonucleotides.
Marcel Veltrop,Laura van Vliet,Margriet Hulsker,Jill W. C. Claassens,Conny Brouwers,Cor Breukel,Jos van der Kaa,Margot M. Linssen,Johan T. den Dunnen,Sjef Verbeek,Annemieke Aartsma-Rus,Maaike van Putten +11 more
TL;DR: The del52hDMD/mdx model enables the in vivo analysis of human specific AONs targeting exon 51 or exon 53 on RNA and protein level and muscle quality and function and will be a valuable tool for optimizing human specificAONs and genome editing approaches for DMD.
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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