Cyclosporin A corrects mitochondrial dysfunction and muscle apoptosis in patients with collagen VI myopathies. (Articolo in rivista)

Type
Label
  • Cyclosporin A corrects mitochondrial dysfunction and muscle apoptosis in patients with collagen VI myopathies. (Articolo in rivista) (literal)
Anno
  • 2008-01-01T00:00:00+01:00 (literal)
Alternative label
  • Merlini L., Angelin A., Tiepolo T., Braghetta P., Sabatelli P., Zamparelli A., Ferlini A., Maraldi N.M., Bonaldo P. and Bernardi P. (2008)
    Cyclosporin A corrects mitochondrial dysfunction and muscle apoptosis in patients with collagen VI myopathies.
    in Proceedings of the National Academy of Sciences of the United States of America
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Merlini L., Angelin A., Tiepolo T., Braghetta P., Sabatelli P., Zamparelli A., Ferlini A., Maraldi N.M., Bonaldo P. and Bernardi P. (literal)
Pagina inizio
  • 5225 (literal)
Pagina fine
  • 5229 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 105 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Department of Experimental and Diagnostic Medicine, Section of Medical Genetics, University of Ferrara, I-44100 Ferrara, Italy; Department of Biomedical Sciences and Consiglio Nazionale delle Ricerche Institute of Neuroscience and Department of Histology, Microbiology, and Medical Biotechnologies, University of Padova, I-35121 Padua, Italy; Istituto di Genetica Molecolare-Consiglio Nazionale delle Ricerche c/o Istituto Ortopedico Rizzoli and the Department of Anatomical Sciences, University of Bologna, I-40136 Bologna, Italy . (literal)
Titolo
  • Cyclosporin A corrects mitochondrial dysfunction and muscle apoptosis in patients with collagen VI myopathies. (literal)
Abstract
  • Ullrich congenital muscular dystrophy and Bethlem myopathy are skeletal muscle diseases that are due to mutations in the genes encoding collagen VI, an extracellular matrix protein forming a microfibrillar network that is particularly prominent in the endomysium of skeletal muscle. Myoblasts from patients affected by Ullrich congenital muscular dystrophy display functional and ultrastructural mitochondrial alterations and increased apoptosis due to inappropriate opening of the permeability transition pore, a mitochondrial inner membrane channel. These alterations could be normalized by treatment with cyclosporin A, a widely used immunosuppressant that desensitizes the permeability transition pore independently of calcineurin inhibition. Here, we report the results of an open pilot trial with cyclosporin A in five patients with collagen VI myopathies. Before treatment, all patients displayed mitochondrial dysfunction and increased frequency of apoptosis, as determined in muscle biopsies. Both of these pathologic signs were largely normalized after 1 month of oral cyclosporin A administration, which also increased muscle regeneration. These findings demonstrate that collagen VI myopathies can be effectively treated with drugs acting on the pathogenic mechanism downstream of the genetic lesion, and they represent an important proof of principle for the potential therapy of genetic diseases. (literal)
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