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
Current Pharmacological Strategies for Duchenne Muscular Dystrophy.
Shanshan Yao,Zihao Chen,Yuanyuan Yu,Ning Zhang,Hewen Jiang,Ge Zhang,Zong-Kang Zhang,Bao-Ting Zhang +7 more
TL;DR: A review of dystrophin-targeted therapeutic strategies for Duchenne muscular dystrophy can be found in this paper, where the rationale and efficacy of each agent in pre-clinical or clinical studies are presented.
Journal ArticleDOI
The administration of antisense oligonucleotide golodirsen reduces pathological regeneration in patients with Duchenne muscular dystrophy
D. Scaglioni,D. Scaglioni,F. Catapano,F. Catapano,F. Catapano,Matthew Ellis,Matthew Ellis,Silvia Torelli,Silvia Torelli,D. Chambers,Lucy Feng,Matthew Beck,Matthew Beck,Caroline Sewry,Mauro Monforte,Shawn Harriman,Erica Koenig,Jyoti Malhotra,Linda Popplewell,Michela Guglieri,Volker Straub,Eugenio Mercuri,Laurent Servais,Rahul Phadke,Jennifer E. Morgan,Jennifer E. Morgan,Francesco Muntoni,Francesco Muntoni +27 more
TL;DR: In this paper, the de novo dystrophin induced by exon skipping with morpholino antisense oligonucleotide (PMO) golodirsen was demonstrated to be capable of conferring a histological benefit in treated patients with an increase in dystrophicin associated proteins at the dystophin positive regions of the sarcolemma in post-treatment biopsies.
Journal ArticleDOI
Toxicological Characterization of Exon Skipping Phosphorodiamidate Morpholino Oligomers (PMOs) in Non-human Primates.
Michael P. Carver,Jay S. Charleston,Courtney Shanks,Jianbo Zhang,Mark G. Mense,Alok K. Sharma,Harjeet Kaur,Peter Sazani +7 more
TL;DR: Nonclinical results in NHPs for these three PMOs, together with the excellent clinical safety established for eteplirsen to date, suggest that once-weekly IV administration of PMOs for lifetime durations at therapeutic doses will be well tolerated by patients with DMD.
Journal ArticleDOI
Persistent Dystrophin Protein Restoration 90 Days after a Course of Intraperitoneally Administered Naked 2 OMePS AON and ZM2 NP-AON Complexes in mdx Mice
Elena Bassi,Sofia Falzarano,M. Fabris,Francesca Gualandi,Luciano Merlini,Gaetano Vattemi,Daniela Perrone,Elena Marchesi,Patrizia Sabatelli,Katia Sparnacci,Michele Laus,Paolo Bonaldo,Paola Rimessi,Paola Braghetta,Alessandra Ferlini +14 more
TL;DR: The long-term residual efficacy of this systemic low-dose treatment of exon-skipping is demonstrated and the protective effect nanoparticles exert on AON molecules is confirmed.
Journal ArticleDOI
Fructose Promotes Uptake and Activity of Oligonucleotides With Different Chemistries in a Context-dependent Manner in mdx Mice
Limin Cao,Limin Cao,Gang Han,Caorui Lin,Ben Gu,Xianjun Gao,Hong M. Moulton,Yiqi Seow,HaiFang Yin +8 more
TL;DR: Fructose can potentiate AOs of different chemistries in vivo although the effect diminished over repeated administration, and it is shown that fructose improved the potency of AOs tested with the greatest effect on phosphorodiamidate morpholino oligomer.
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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