Effects of an immunosuppressive treatment in the GRMD dog model of Duchenne muscular dystrophy

Autor: Carole Drougard, Jean-Laurent Thibaud, Inès Barthélémy, Stéphane Blot, Yves Unterfinger, Ane Uriarte
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Anatomy and Physiology
Muscle Functions
Duchenne muscular dystrophy
lcsh:Medicine
Disease
Muscular Dystrophies
Accelerometry
Biomechanics
Muscular dystrophy
lcsh:Science
Musculoskeletal System
Creatine Kinase
Gait
Principal Component Analysis
Tetany
Multidisciplinary
biology
medicine.diagnostic_test
Neuromuscular Diseases
Biomechanical Phenomena
Neurology
Cyclosporine
Prednisolone
Muscle
Medicine
medicine.symptom
Immunosuppressive Agents
Research Article
medicine.drug
medicine.medical_specialty
Clinical Research Design
Motor Activity
Immune Suppression
Dogs
Pharmacotherapy
Internal medicine
Biopsy
medicine
Animals
Humans
Animal Models of Disease
Biology
business.industry
lcsh:R
Immunity
Muscular Dystrophy
Animal
medicine.disease
Surgery
Muscular Dystrophy
Duchenne
Disease Models
Animal
biology.protein
Clinical Immunology
Creatine kinase
lcsh:Q
business
Follow-Up Studies
Zdroj: PLoS ONE, Vol 7, Iss 11, p e48478 (2012)
PLoS ONE
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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