Hua Yu

Publications (3)16.52 Total impact

• Article: Arginine butyrate: a therapeutic candidate for Duchenne muscular dystrophy.

  Sara Vianello, Hua Yu, Vincent Voisin, Hafedh Haddad, Xun He, Arthur S Foutz, Catherine Sebrié, Brigitte Gillet, Morgane Roulot, Françoise Fougerousse, Caroline Perronnet, Cyrille Vaillend, Stefan Matecki, Diana Escolar, Laura Bossi, Maurice Israël, Sabine de la Porte
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  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 (EC(50)=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.
  The FASEB Journal 02/2013; · 5.71 Impact Factor
• Article: MALDI reveals membrane lipid profile reversion in MDX mice.

  Farida Benabdellah, Hua Yu, Alain Brunelle, Olivier Laprévote, Sabine De La Porte
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  ABSTRACT: Duchenne muscular dystrophy (DMD), the most common and severe X-linked myopathy, is characterized by the lack of dystrophin, a sub-sarcolemmal protein necessary for normal muscle functions. In a previous study of the lipid content of skeletal muscles of dystrophic (mdx) mice, the animal model for DMD, by in situ Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry (MALDI-MS), an inversion of the phosphatidylcholine PC34:2/PC34:1 ion peaks intensity ratio was observed between destructured (abnormal fiber morphology) and structured (normal fiber morphology). A possible treatment for this dramatic disease is to introduce an exogenous nitric oxide (NO) donor into the organism, leading to an increase of utrophin and a regression of the dystrophic phenotype. In the present work, after confirmation by tandem mass spectrometry of the structure of these two phospholipids, their intensity ratio inversion was used to evidence a restoration of membrane lipid composition very similar to those of wild-type mice after the treatment of mdx mice with molsidomine, a NO donor. This was associated with the observation by immunohistology of an increase of the regeneration process in the mice.
  Neurobiology of Disease 08/2009; 36(2):252-8. · 5.40 Impact Factor
• Article: L-arginine improves dystrophic phenotype in mdx mice.

  Vincent Voisin, Catherine Sébrié, Stéfan Matecki, Hua Yu, Brigitte Gillet, Michèle Ramonatxo, Maurice Israël, Sabine De la Porte
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  ABSTRACT: A possible treatment for Duchenne muscular dystrophies would be to compensate for dystrophin loss by increasing the expression of utrophin, another cytoskeletal protein of the muscle membrane. We previously found that L-arginine, the substrate for nitric oxide synthase, significantly increased utrophin level in muscle and targeted it to the sarcolemma. Here, we have addressed the expected benefit in the mdx mice. Magnetic resonance imaging of lower limbs revealed a 35% reduction of the necrotic zones, confirmed by histological staining of muscles. This regression of the necrosis was also supported by the drastic reduction of Evans blue incorporation, a cell impermeable dye. The creatine kinase level in the serum decreased by 57%. Utrophin level increased 2- to 3-fold in muscles. Beta-dystroglycan was relocalised with utrophin to the membrane. In the diaphragm, the most affected muscle in mdx mice, the isometric tension increased by 30%, with regression of collagen and of cytoplasmic lipid overloading. Finally, molsidomine, a therapeutic agent that is converted to a NO donor, also attenuated the dystrophic phenotype. Our results suggest that pharmacological activators of the NO pathway may constitute a realistic treatment for Duchenne and Becker muscular dystrophies.
  Neurobiology of Disease 11/2005; 20(1):123-30. · 5.40 Impact Factor