T.O.1 Functional evaluation of dystrophic dogs treated by exon-skipping

Barthélémy, I.; Thibaud, Jean-Laurent; Vulin, Adeline; Bertoldi, D.; Goyenvalle, Aurélie; Lorrain, S.; Dreyfus, Patrick A.; Carlier, P.; Garcı́a, Luis; Blot, Stéphane

doi:10.1016/j.nmd.2007.06.456

Cited by 4 publications

(2 citation statements)

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“…Briefly the dogs were anaesthetized, following the same protocol as for the muscle biopsies. They were positioned in dorsal recumbency and both their hindlimbs were successively positioned into a dedicated device already used to assess muscle force after therapeutic procedures [5] , [26] . The device is composed of two force transducers (Grass transducers FT10) linked to a vertical plate supporting the anatomical segment encompassing the tarsus, metatarsus and digits.…”

Section: Methodsmentioning

confidence: 99%

Effects of an Immunosuppressive Treatment in the GRMD Dog Model of Duchenne Muscular Dystrophy

Barthélémy¹,

Uriarte

Drougard³

et al. 2012

PLoS ONE

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The GRMD (Golden retriever muscular dystrophy) dog has been widely used in pre-clinical trials targeting DMD (Duchenne muscular dystrophy), using in many cases a concurrent immune-suppressive treatment. The aim of this study is to assess if such a treatment could have an effect on the disease course of these animals. Seven GRMD dogs were treated with an association of cyclosporine A (immunosuppressive dosage) and prednisolone (2 mg/kg/d) during 7 months, from 2 to 9 months of age. A multi-parametric evaluation was performed during this period which allowed us to demonstrate that this treatment had several significant effects on the disease progression. The gait quality as assessed by 3D-accelerometry was dramatically improved. This was consistent with the evolution of other parameters towards a significant improvement, such as the clinical motor score, the post-tetanic relaxation and the serum CK levels. In contrast the isometric force measurement as well as the histological evaluation argued in favor of a more severe disease progression. In view of the disease modifying effects which have been observed in this study it should be concluded that immunosuppressive treatments should be used with caution when carrying out pre-clinical studies in this canine model of DMD. They also highlight the importance of using a large range of multi-parametric evaluation tools to reliably draw any conclusion from trials involving dystrophin-deficient dogs, which reproduce the complexity of the human disease.

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Section: Methodsmentioning

confidence: 99%

Effects of an Immunosuppressive Treatment in the GRMD Dog Model of Duchenne Muscular Dystrophy

Barthélémy¹,

Uriarte

Drougard³

et al. 2012

PLoS ONE

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“…A continuous monitoring of ECG, SpO2, ETCO2, rectal temperature was set up, and an automatic ventilator was used to maintain normocapnia. They were positioned in dorsal recumbency and their both hindlimbs were successively positioned into a dedicated device already used to assess muscle force after therapeutic procedures [42,51]. The device was composed of two force transducers (HBM PW6DC3) linked to a vertical plate supporting the anatomical segment encompassing the tarsus, metatarsus and digits.…”

Section: Force Measurementmentioning

confidence: 99%

X-linked muscular dystrophy in a Labrador Retriever strain: phenotypic and molecular characterization.

Barthélémy

Calmels

et al. 2020

Preprint

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Background Canine models of Duchenne muscular dystrophy (DMD) are valuable to evaluate therapies because they faithfully reproduce the human disease. Several cases of dystrophinopathies have been described in canines, but the GRMD (Golden Retriever Muscular Dystrophy) model remains the one used in most preclinical studies. Methods We report a new spontaneous dystrophinopathy in a Labrador retriever strain, named LRMD (Labrador Retriever Muscular Dystrophy), for which a colony was established. Fourteen LRMD dogs were followed-up and compared to the GRMD standard. Results The clinical features of the GRMD disease were found in LRMD dogs, and the functional tests provided data roughly overlapping those measured in GRMD dogs, with similar inter-individual heterogeneity. Molecular techniques including RNA-sequencing allowed to map and identify the LRMD causal mutation, consisting in a 2.2-Mb inversion disrupting the DMD gene within its intron 20, and involving TMEM47 gene. In skeletal muscles, the Dp71 isoform was ectopically expressed as a probable consequence of the mutation. We found no evidence of polymorphism in the two LTBP4 and Jagged1 modifier genes that would explain the observed inter-individual variability. Conclusions This study provides a full comparative description of a new spontaneous canine dystrophinopathy, that we demonstrate is phenotypically equivalent to the GRMD model. We report a novel large DNA mutation within the DMD gene and provide evidence that LRMD is a relevant model to pinpoint additional DMD modifier genes.

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Évaluation par résonance magnétique nucléaire du muscle strié squelettique et cardiaque du chien déficient en dystrophine

Thibaud

Wary

Barthélémy

et al. 2011

Pratique Médicale et Chirurgicale de l'Animal de Compagnie

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T.O.1 Functional evaluation of dystrophic dogs treated by exon-skipping

Cited by 4 publications

References 0 publications

Effects of an Immunosuppressive Treatment in the GRMD Dog Model of Duchenne Muscular Dystrophy

Effects of an Immunosuppressive Treatment in the GRMD Dog Model of Duchenne Muscular Dystrophy

X-linked muscular dystrophy in a Labrador Retriever strain: phenotypic and molecular characterization.

Évaluation par résonance magnétique nucléaire du muscle strié squelettique et cardiaque du chien déficient en dystrophine

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