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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Journal ArticleDOI
Advances in the Treatment of Duchenne Muscular Dystrophy: New and Emerging Pharmacotherapies.
TL;DR: An update on the medications being investigated in DMD is provided, including stop codon readthrough agents, exon‐skipping agents, and utrophin modulators, which aim to replace dystrophin in myocytes.
Journal ArticleDOI
Rapamycin nanoparticles target defective autophagy in muscular dystrophy to enhance both strength and cardiac function
Kristin P. Bibee,Ya-Jian Cheng,James Kain Ching,Jon N. Marsh,Allison Jinquan Li,Richard M. Keeling,Anne M. Connolly,Paul T. Golumbek,Jacob W. Myerson,Grace Hu,Junjie Chen,William D. Shannon,Gregory M. Lanza,Conrad C. Weihl,Samuel A. Wickline +14 more
TL;DR: It is demonstrated that alternative approaches that rescue defective autophagy in mdx mice, a model of Duchenne muscular dystrophy, with the use of rapamycin‐loaded nanoparticles induce a reproducible increase in both skeletal muscle strength and cardiac contractile performance that is not achievable with conventional oral rapamyin, even in pharmacological doses.
Journal ArticleDOI
Functional Rescue of Dystrophin Deficiency in Mice Caused by Frameshift Mutations Using Campylobacter jejuni Cas9.
Taeyoung Koo,Ngoc Lu-Nguyen,Alberto Malerba,Eunji Kim,Daesik Kim,Ornella Cappellari,Hee-Yeon Cho,George Dickson,Linda Popplewell,Jin-Soo Kim +9 more
TL;DR: It is shown that CjCas9 derived from Campylobacter jejuni can be used as a gene-editing tool to correct an out-of-frame DMD exon in DMD knockout mice, and muscle strength was enhanced in the Cj Cas9-treated muscles, without off-target mutations, indicating high efficiency and specificity of CJCas9.
Journal ArticleDOI
Morpholino antisense oligonucleotides targeting intronic repressor Element1 improve phenotype in SMA mouse models
Erkan Y. Osman,Madeline R. Miller,Kate L. Robbins,Abby M. Lombardi,Arleigh K. Atkinson,Amanda J. Brehm,Christian L. Lorson +6 more
TL;DR: To prevent exon-skipping, the development of E1 ASOs provides a new molecular target for SMA therapeutics that dramatically extends survival in two important pre-clinical models of disease.
Journal ArticleDOI
What has the mdx mouse model of Duchenne muscular dystrophy contributed to our understanding of this disease
Jennifer Manning,Dervla O'Malley +1 more
TL;DR: This review explores what has learned from this dystrophin-deficient mdx mouse model regarding the pathophysiology of DMD and asks if it has a future in providing a better more thorough understanding of this disease or if it will bring us any closer to improving the outlook for DMD patients.
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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Local restoration of dystrophin expression with the morpholino oligomer AVI-4658 in Duchenne muscular dystrophy: a single-blind, placebo-controlled, dose-escalation, proof-of-concept study
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