{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:34:00Z","timestamp":1791473640570,"version":"4.3.4"},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T00:00:00Z","timestamp":1523836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005693","name":"Parent Project Muscular Dystrophy","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005693","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["113302001"],"award-info":[{"award-number":["113302001"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Analysis of muscle biopsies allowed to characterize the pathophysiological changes of Duchenne and Becker muscular dystrophies (D\/BMD) leading to the clinical phenotype. Muscle tissue is often investigated during interventional dose finding studies to show <jats:italic>in situ<\/jats:italic> proof of concept and pharmacodynamics effect of the tested drug. Less invasive readouts are needed to objectively monitor patients' health status, muscle quality, and response to treatment. The identification of serum biomarkers correlating with clinical function and able to anticipate functional scales is particularly needed for personalized patient management and to support drug development programs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A large\u2010scale proteomic approach was used to identify serum biomarkers describing pathophysiological changes (e.g. loss of muscle mass), association with clinical function, prediction of disease milestones, association with <jats:italic>in vivo<\/jats:italic> <jats:sup>31<\/jats:sup>P magnetic resonance spectroscopy data and dystrophin levels in muscles. Cross\u2010sectional comparisons were performed to compare DMD patients, BMD patients, and healthy controls. A group of DMD patients was followed up for a median of 4.4\u00a0years to allow monitoring of individual disease trajectories based on yearly visits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cross\u2010sectional comparison enabled to identify 10 proteins discriminating between healthy controls, DMD and BMD patients. Several proteins (285) were able to separate DMD from healthy, while 121 proteins differentiated between BMD and DMD; only 13 proteins separated BMD and healthy individuals. The concentration of specific proteins in serum was significantly associated with patients' performance (e.g. BMP6 serum levels and elbow flexion) or dystrophin levels (e.g. TIMP2) in BMD patients. Analysis of longitudinal trajectories allowed to identify 427 proteins affected over time indicating loss of muscle mass, replacement of muscle by adipose tissue, and cardiac involvement. Over\u2010representation analysis of longitudinal data allowed to highlight proteins that could be used as pharmacodynamic biomarkers for drugs currently in clinical development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Serum proteomic analysis allowed to not only discriminate among DMD, BMD, and healthy subjects, but it enabled to detect significant associations with clinical function, dystrophin levels, and disease progression.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12304","type":"journal-article","created":{"date-parts":[[2018,4,23]],"date-time":"2018-04-23T08:34:53Z","timestamp":1524472493000},"page":"715-726","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Tracking disease progression non\u2010invasively in Duchenne and Becker muscular dystrophies"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2783-688X","authenticated-orcid":false,"given":"Pietro","family":"Spitali","sequence":"first","affiliation":[{"name":"Department of Human Genetics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Hettne","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roula","family":"Tsonaka","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics and Bioinformatics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Charrout","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janneke","family":"van den Bergen","sequence":"additional","affiliation":[{"name":"Department of Neurology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Za\u00efda","family":"Koeks","sequence":"additional","affiliation":[{"name":"Department of Neurology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermien E.","family":"Kan","sequence":"additional","affiliation":[{"name":"C.J. Gorter Center for High Field MRI, Department of Radiology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa T.","family":"Hooijmans","sequence":"additional","affiliation":[{"name":"C.J. Gorter Center for High Field MRI, Department of Radiology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Roos","sequence":"additional","affiliation":[{"name":"John Walton Muscular Dystrophy Research Centre, MRC Centre for Neuromuscular Diseases, Institute of Genetic Medicine University of Newcastle  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Straub","sequence":"additional","affiliation":[{"name":"John Walton Muscular Dystrophy Research Centre, MRC Centre for Neuromuscular Diseases, Institute of Genetic Medicine University of Newcastle  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Muntoni","sequence":"additional","affiliation":[{"name":"Dubowitz Neuromuscular Centre University College London Great Ormond Street Institute of Child Health  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Al\u2010Khalili\u2010Szigyarto","sequence":"additional","affiliation":[{"name":"Division of Proteomics, School of Biotechnology KTH\u2014Royal Institute of Technology  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marleen J.A.","family":"Koel\u2010Simmelink","sequence":"additional","affiliation":[{"name":"Neurochemistry Lab and Biobank, Department of Clinical Chemistry, Amsterdam Neuroscience VU University Medical Center Amsterdam  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte E.","family":"Teunissen","sequence":"additional","affiliation":[{"name":"Neurochemistry Lab and Biobank, Department of Clinical Chemistry, Amsterdam Neuroscience VU University Medical Center Amsterdam  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanns","family":"Lochm\u00fcller","sequence":"additional","affiliation":[{"name":"John Walton Muscular Dystrophy Research Centre, MRC Centre for Neuromuscular Diseases, Institute of Genetic Medicine University of Newcastle  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik H.","family":"Niks","sequence":"additional","affiliation":[{"name":"Department of Neurology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemieke","family":"Aartsma\u2010Rus","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Leiden University Medical Center  Leiden The Netherlands"},{"name":"C.J. 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