Arginine butyrate: a therapeutic candidate for Duchenne muscular dystrophy

Autor: Arthur S. Foutz, Diana M. Escolar, Hafedh Haddad, Morgane Roulot, Vincent Voisin, Catherine Sebrié, Xun He, Hua Yu, Sara Vianello, Sabine De La Porte, Maurice Israël, Brigitte Gillet, Stefan Matecki, Cyrille Vaillend, Françoise Fougerousse, Laura Bossi, Caroline Perronnet
Přispěvatelé: Institut de Neurobiologie Alfred Fessard (INAF), Centre National de la Recherche Scientifique (CNRS), Neurobiologie & Développement (N&D), Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Généthon, Centre de Neurosciences Paris-Sud (CNPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Johns Hopkins School of Medicine, PERIGNON, Alain, Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Male
Utrophin
Duchenne muscular dystrophy
Muscle Fibers
Skeletal
MESH: Butyrates
Biochemistry
MESH: Muscular Dystrophy
Animal
MESH: Animals
Newborn
MESH: Drug Synergism
Mice
0302 clinical medicine
MESH: Up-Regulation
MESH: Animals
Muscular dystrophy
MESH: Histone Deacetylase Inhibitors
Cells
Cultured
ComputingMilieux_MISCELLANEOUS
0303 health sciences
MESH: Muscle Fibers
Skeletal
biology
[CHIM.ORGA]Chemical Sciences/Organic chemistry
Myogenesis
MESH: Mice
Inbred mdx
MESH: Arginine
Drug Synergism
Up-Regulation
3. Good health
Butyrates
medicine.anatomical_structure
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Dystrophin
Biotechnology
MESH: Cells
Cultured
medicine.medical_specialty
Arginine
03 medical and health sciences
MESH: Utrophin
In vivo
MESH: Mice
Inbred C57BL
Internal medicine
Genetics
medicine
MESH: Muscular Dystrophy
Duchenne
Animals
Humans
[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Molecular Biology
MESH: Mice
030304 developmental biology
MESH: Humans
Skeletal muscle
Muscular Dystrophy
Animal
medicine.disease
MESH: Male
Histone Deacetylase Inhibitors
Mice
Inbred C57BL
Muscular Dystrophy
Duchenne
Endocrinology
Animals
Newborn
Mice
Inbred mdx
biology.protein
Creatine kinase
030217 neurology & neurosurgery
Zdroj: FASEB Journal
FASEB Journal, Federation of American Society of Experimental Biology, 2013, 27 (6), pp.2256-69. ⟨10.1096/fj.12-215723⟩
FASEB Journal, Federation of American Society of Experimental Biology, 2013, 27 (6), pp.2256-2269. ⟨10.1096/fj.12-215723⟩
FASEB Journal, 2013, 27 (6), pp.2256-69. ⟨10.1096/fj.12-215723⟩
ISSN: 0892-6638
1530-6860
DOI: 10.1096/fj.12-215723⟩
Popis: International audience; 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.
Databáze: OpenAIRE
Externí odkaz: