Article (Scientific journals)
Long-term microdystrophin gene therapy is effective in a canine model of Duchenne muscular dystrophy.
Le Guiner, Caroline; Servais, Laurent; Montus, Marie et al.
2017In Nature Communications, 8, p. 16105
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Abstract :
[en] Duchenne muscular dystrophy (DMD) is an incurable X-linked muscle-wasting disease caused by mutations in the dystrophin gene. Gene therapy using highly functional microdystrophin genes and recombinant adeno-associated virus (rAAV) vectors is an attractive strategy to treat DMD. Here we show that locoregional and systemic delivery of a rAAV2/8 vector expressing a canine microdystrophin (cMD1) is effective in restoring dystrophin expression and stabilizing clinical symptoms in studies performed on a total of 12 treated golden retriever muscular dystrophy (GRMD) dogs. Locoregional delivery induces high levels of microdystrophin expression in limb musculature and significant amelioration of histological and functional parameters. Systemic intravenous administration without immunosuppression results in significant and sustained levels of microdystrophin in skeletal muscles and reduces dystrophic symptoms for over 2 years. No toxicity or adverse immune consequences of vector administration are observed. These studies indicate safety and efficacy of systemic rAAV-cMD1 delivery in a large animal model of DMD, and pave the way towards clinical trials of rAAV-microdystrophin gene therapy in DMD patients.
Disciplines :
Neurology
Author, co-author :
Le Guiner, Caroline
Servais, Laurent ;  Université de Liège - ULiège > Département des sciences cliniques > Neuropédiatrie
Montus, Marie
Larcher, Thibaut
Fraysse, Bodvael
Moullec, Sophie
Allais, Marine
Francois, Virginie
Dutilleul, Maeva
Malerba, Alberto
Koo, Taeyoung
Thibaut, Jean-Laurent
Matot, Beatrice
Devaux, Marie
Le Duff, Johanne
Deschamps, Jack-Yves
Barthelemy, Ines
Blot, Stephane
Testault, Isabelle
Wahbi, Karim
Ederhy, Stephane
Martin, Samia
Veron, Philippe
Georger, Christophe
Athanasopoulos, Takis
Masurier, Carole
Mingozzi, Federico
Carlier, Pierre
Gjata, Bernard
Hogrel, Jean-Yves
Adjali, Oumeya
Mavilio, Fulvio
Voit, Thomas
Moullier, Philippe
Dickson, George
More authors (25 more) Less
Language :
English
Title :
Long-term microdystrophin gene therapy is effective in a canine model of Duchenne muscular dystrophy.
Publication date :
July 2017
Journal title :
Nature Communications
eISSN :
2041-1723
Publisher :
Nature Publishing Group, United Kingdom
Volume :
8
Pages :
16105
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 14 February 2018

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