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
Antisense-mediated exon skipping: a therapeutic strategy for titin-based dilated cardiomyopathy
Michael Gramlich,Luna Simona Pane,Qifeng Zhou,Zhifen Chen,Marta Murgia,Sonja Schötterl,Alexander Goedel,Katja Metzger,Thomas Brade,Elvira Immacolata Parrotta,Elvira Immacolata Parrotta,Martin Schaller,Brenda Gerull,Ludwig Thierfelder,Annemieke Aartsma-Rus,Siegfried Labeit,John Atherton,Julie McGaughran,Richard P. Harvey,Richard P. Harvey,Daniel Sinnecker,Matthias Mann,Karl-Ludwig Laugwitz,Meinrad Gawaz,Alessandra Moretti +24 more
TL;DR: It is demonstrated that disruption of the titin reading frame due to a truncating DCM mutation can be restored by exon skipping in both patient cardiomyocytes in vitro and mouse heart in vivo, indicating RNA‐based strategies as a potential treatment option for DCM.
Journal ArticleDOI
Dystrophin levels and clinical severity in Becker muscular dystrophy patients
J.C. van den Bergen,B.H.A. Wokke,Anneke A.M. Janson,S. G. Van Duinen,Margriet Hulsker,H.B. Ginjaar,J C van Deutekom,Annemieke Aartsma-Rus,Hermien E. Kan,Jan J.G.M. Verschuuren +9 more
TL;DR: Dystrophin levels appear not to be a major determinant of disease severity in BMD, as long as it is above approximately 10%, which suggests that the disease course depends more on the mutation site than on the amount of the dystrophic protein produced.
Journal ArticleDOI
Spell Checking Nature: Versatility of CRISPR/Cas9 for Developing Treatments for Inherited Disorders
Daria Wojtal,Dwi U. Kemaladewi,Zeenat Malam,Sarah Abdullah,Tatianna Wai Ying Wong,Elzbieta Hyatt,Zahra Baghestani,Sergio L. Pereira,Sergio L. Pereira,James Stavropoulos,Vincent Mouly,Kamel Mamchaoui,Francesco Muntoni,Thomas Voit,Hernan Gonorazky,James J. Dowling,Michael D. Wilson,Roberto Mendoza-Londono,Evgueni A. Ivakine,Ronald D. Cohn +19 more
TL;DR: It is shown that an adapted version of CRISPR/Cas9 increases the amount of utrophin, a known disease modifier in Duchenne muscular dystrophy (DMD), and a previously undescribed approach involving single guide RNA is successfully removed large genome rearrangement in primary cells of an individual with an X chromosome duplication including MECP2.
Journal ArticleDOI
What Can We Learn From Clinical Trials of Exon Skipping for DMD
TL;DR: The clinical trial results and the FDA's view of the relationship between the dystrophin biomarker and functional endpoint of 6MWT in clinic will have a far reaching impact beyond exon skipping therapy in DMD.
Journal ArticleDOI
Low dystrophin levels increase survival and improve muscle pathology and function in dystrophin/utrophin double-knockout mice
Maaike van Putten,Margriet Hulsker,Courtney S. Young,Vishna Devi Nadarajah,Hans Heemskerk,Louise van der Weerd,Peter A C 't Hoen,Gert-Jan B. van Ommen,Annemieke Aartsma-Rus +8 more
TL;DR: It is suggested that the dystrophin levels needed to benefit vitality and functioning of patients with DMD might be lower than those needed for full protection against muscle damage.
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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