Serum proteomic profiling reveals fragments of MYOM3 as potential biomarkers for monitoring the outcome of therapeutic interventions in muscular dystrophies
| Autor: | GARCIA, Luis, Rouillon, Jeremy, Poupiot, Jérôme, Zocevic, Aleksandar, Amor, Fatima, Léger, Thibaut, Garcia, Camille, Camadro, Jean-Michel, Wong, Brenda, Pinilla, Robin, Cosette, Jérémie, Coenen-Stass, Anna M.L., Mcclorey, Graham, Roberts, Thomas, Wood, Matthew J.A., Servais, Laurent, Udd, Bjarne, Voit, Thomas, Richard, Isabelle, Svinartchouk, Fedor |
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| Přispěvatelé: | Centre de recherche et d'applications sur les thérapies géniques (CRATG), Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS)-Généthon, Généthon, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Division of Pediatric Neurology, Cincinnati Children's Hospital Medical Center, South Parks Road, Department of Physiology, Anatomy and Genetics, University of Oxford, University of Oxford [Oxford], Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Pierre et Marie Curie - Paris 6 (UPMC), University of Helsinki, Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Department of Physiology, Anatomy and Genetics [Oxford], The Scripps Research Institute [La Jolla], University of California [San Diego] (UC San Diego), University of California-University of California, Department of Medical and Clinical Genetics [Helsinki], Haartman Institute [Helsinki], Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Association Française contre les Myopathies (AFM), French public agency OSEO, Genethon, École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon, University of Oxford, The Scripps Research Institute [La Jolla, San Diego], Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Université d'Évry-Val-d'Essonne (UEVE)-GENETHON 3-Centre National de la Recherche Scientifique (CNRS), Généthon, Evry, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École pratique des hautes études (EPHE)-Université d'Évry-Val-d'Essonne (UEVE)-GENETHON 3-Institut National de la Santé et de la Recherche Médicale (INSERM), The Scripps Research Institute [San Diego], Lääketieteen yksikkö - School of Medicine, University of Tampere, Department of Medical and Clinical Genetics, Medicum |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Proteomics
mdx mouse Duchenne muscular dystrophy [SDV]Life Sciences [q-bio] Bioinformatics Mass Spectrometry Muscular Dystrophies Mice MEMBRANE REPAIR Connectin Muscular dystrophy Child Creatine Kinase Genetics (clinical) ComputingMilieux_MISCELLANEOUS GENE-EXPRESSION medicine.diagnostic_test MDX MOUSE Articles Blood Proteins General Medicine M-BAND Treatment Outcome Child Preschool SKELETAL-MUSCLE 3-METHYLHISTIDINE EXCRETION Dystrophin Neurotieteet - Neurosciences Adult musculoskeletal diseases Adolescent Biology PHENOTYPIC CORRECTION Young Adult Western blot MYOFIBRILLAR PROTEIN CATABOLISM CREATINE-KINASE CK Genetics medicine Animals Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Molecular Biology [SDV.GEN]Life Sciences [q-bio]/Genetics Proteomic Profiling medicine.disease Molecular biology Muscular Dystrophy Duchenne Disease Models Animal Case-Control Studies Mice Inbred mdx biology.protein Creatine kinase 3111 Biomedicine SARCOGLYCAN DEFICIENCY Biomarkers |
| Zdroj: | Human Molecular Genetics Human Molecular Genetics, Oxford University Press (OUP), 2015, 24 (17), pp.4916-4932. ⟨10.1093/hmg/ddv214⟩ Human Molecular Genetics, 2015, 24 (17), pp.4916-4932. ⟨10.1093/hmg/ddv214⟩ |
| ISSN: | 0964-6906 1460-2083 |
| Popis: | International audience; Therapy-responsive biomarkers are an important and unmet need in the muscular dystrophy field where new treatments are currently in clinical trials. By using a comprehensive high-resolution mass spectrometry approach and western blot validation, we found that two fragments of the myofibrillar structural protein myomesin-3 (MYOM3) are abnormally present in sera of Duchenne muscular dystrophy (DMD) patients, limb-girdle muscular dystrophy type 2D (LGMD2D) and their respective animal models. Levels of MYOM3 fragments were assayed in therapeutic model systems: (1) restoration of dystrophin expression by antisense oligonucleotide-mediated exon-skipping in mdx mice and (2) stable restoration of α-sarcoglycan expression in KO-SGCA mice by systemic injection of a viral vector. Following administration of the therapeutic agents MYOM3 was restored toward wild-type levels. In the LGMD model, where different doses of vector were used, MYOM3 restoration was dose-dependent. MYOM3 fragments showed lower inter-individual variability compared with the commonly used creatine kinase assay, and correlated better with the restoration of the dystrophin-associated protein complex and muscle force. These data suggest that the MYOM3 fragments hold promise for minimally invasive assessment of experimental therapies for DMD and other neuromuscular disorders. |
| Databáze: | OpenAIRE |
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