Publications

Dernière publication 21/02/2013

Arginine butyrate- a therapeutic candidate for Duchenne muscular dystrophy-

As a strategy to treat Duchenne muscular dystrophy, we used arginine butyrate, which combines two pharmacological activities: nitric oxide pathway...

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    [title] => Arginine butyrate- a therapeutic candidate for Duchenne muscular dystrophy-
    [paragraph] => Arginine butyrate: a therapeutic candidate for Duchenne muscular dystrophy.
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Authors
S. Vianello, H. Yu, V. Voisin, H. Haddad, X. He et al

 Lab
Centre National de la Recherche Scientifique (CNRS), Institut de Neurobiologie Alfred Fessard-FRC2118, Gif sur Yvette, France
Journal
The FASEB Journal 
Abstract
As a strategy to treat Duchenne muscular dystrophy, we used arginine butyrate, which combines two pharmacological activities: nitric oxide pathway activation, and histone deacetylase inhibition. Continuous intraperitoneal administration to dystrophin-deficient mdx mice resulted in a near 2-fold increase in utrophin (protein homologous to dystrophin) in skeletal muscle, heart, and brain, accompanied by an improvement of the dystrophic phenotype in both adult and newborn mice (45 and 70% decrease in creatine kinase level, respectively; 14% increase in tidal volume, 30% decrease in necrotic area in limb and 23% increase in isometric force). Intermittent administration, as performed in clinical trials, was then used to reduce the frequency of injections and to improve safety. This also enhanced utrophin level around 2-fold (EC50=284 mg/ml) and alleviated the dystrophic phenotype (inverted grid and grip test performance near to wild-type values, creatine kinase level decreased by 50%). Skin biopsies were used to monitor treatment efficacy, instead of invasive muscle biopsies, and this could be done a few days after the start of treatment. A 2-fold increase in utrophin expression was also shown in cultured human myotubes. In vivo and in vitro experiments demonstrated that the drug combination acts synergistically. Together, these data constitute a proof of principle of the beneficial effects of arginine butyrate on muscular dystrophy.—Vianello, S., Yu, H., Voisin, V., Haddad, H., He, X., Foutz, A. S., Sebrié, C., Gillet, B., Roulot, M., Fougerousse, F., Perronnet, C., Vaillend, C., Matecki, S., Escolar, D., Bossi, L., Israël, M., de la Porte, S. Arginine butyrate: a therapeutic candidate for Duchenne muscular dystrophy.
BIOSEB Instruments Used
Grip strength test (BIO-GS3)

Keywords/Topics
Myopathie de Duchenne; Système musculaire
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Une méthode simple pour quantifier objectivement la force musculaire des rats et souris et l'effet de drogues, toxines, maladies musculaires (ex: myopathie) et neurodégénératives. Cette mesure de force est souvent employée en association avec le test de coordination motrice ROTAROD: un sujet présentant une coordination normale montrera des résultats médiocres en cas de faible force musculaire. Un must pour vos recherches sur l'activité, la coordination et le contrôle musculaire: particulièrement utile pour vos études sur les maladies de Parkinson et Huntington.
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