Cyclosporin A corrects mitochondrial dysfunction and muscle apoptosis in patients with collagen VI myopathies
| العنوان: | Cyclosporin A corrects mitochondrial dysfunction and muscle apoptosis in patients with collagen VI myopathies |
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| المؤلفون: | Tania Tiepolo, Nadir M. Maraldi, Patrizia Sabatelli, Paolo Bernardi, Luciano Merlini, Paolo Bonaldo, Paola Braghetta, Alessandra Ferlini, Alessandra Zamparelli, Alessia Angelin |
| المساهمون: | Merlini L, Angelin A, Tiepolo T, Braghetta P, Sabatelli P, Zamparelli A, Ferlini A, Maraldi NM, Bonaldo P, Bernardi P. |
| المصدر: | Proceedings of the National Academy of Sciences. 105:5225-5229 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Mitochondria, Muscular dystrophy, Apoptosis, Adult, Pathology, medicine.medical_specialty, mitochondria, muscular dystrophy, Ullrich congenital muscular dystrophy, Biopsy, Collagen Type VI, Biology, Mice, Muscular Diseases, Collagen VI, Cyclosporin a, medicine, Animals, Humans, Myocyte, Child, Mice, Knockout, Multidisciplinary, Bethlem myopathy, Skeletal muscle, Anatomy, Biological Sciences, Middle Aged, medicine.disease, medicine.anatomical_structure, Cyclosporine, ITGA7 |
| الوصف: | 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. |
| وصف الملف: | STAMPA |
| تدمد: | 1091-6490 0027-8424 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d64e8f124f25dcaadbba87435a3ed800Test https://doi.org/10.1073/pnas.0800962105Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d64e8f124f25dcaadbba87435a3ed800 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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