{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:34:01Z","timestamp":1791473641683,"version":"4.3.4"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"15","license":[{"start":{"date-parts":[[2020,6,27]],"date-time":"2020-06-27T00:00:00Z","timestamp":1593216000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Commission Horizons 2020","award":["667078"],"award-info":[{"award-number":["667078"]}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["5U54HD090254"],"award-info":[{"award-number":["5U54HD090254"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institutes of Neurologic Disorders and Stroke","award":["R44NS095423"],"award-info":[{"award-number":["R44NS095423"]}]},{"DOI":"10.13039\/100001625","name":"Foundation to Eradicate Duchenne","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001625","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,29]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Duchenne muscular dystrophy (DMD) is caused by loss of dystrophin in muscle, and while all patients share the primary gene and biochemical defect, there is considerable patient\u2013patient variability in clinical symptoms. We sought to develop multivariate models of serum protein biomarkers that explained observed variation, using functional outcome measures as proxies for severity. Serum samples from 39 steroid-na\u00efve DMD boys 4 to &amp;lt;7\u00a0years enrolled into a clinical trial of vamorolone were studied (NCT02760264). Four assessments of gross motor function were carried out for each participant over a 6-week interval, and their mean was used as response for biomarker models. Weighted correlation network analysis was used for unsupervised clustering of 1305 proteins quantified using SOMAscan\u00ae aptamer profiling to define highly representative and connected proteins. Multivariate models of biomarkers were obtained for time to stand performance (strength phenotype; 17 proteins) and 6 min walk performance (endurance phenotype; 17 proteins) including some shared proteins. Identified proteins were tested with associations of mRNA expression with histological severity of muscle from dystrophinopathy patients (n\u2009=\u200928) and normal controls (n\u2009=\u20096). Strong associations predictive of both clinical and histological severity were found for ERBB4 (reductions in both blood and muscle with increasing severity), SOD1 (reductions in muscle and increases in blood with increasing severity) and CNTF (decreased levels in blood and muscle with increasing severity). We show that performance of DMD boys was effectively modeled with serum proteins, proximal strength associated with growth and remodeling pathways and muscle endurance centered on TGF\u03b2 and fibrosis pathways in muscle.<\/jats:p>","DOI":"10.1093\/hmg\/ddaa132","type":"journal-article","created":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T19:15:23Z","timestamp":1593026123000},"page":"2481-2495","source":"Crossref","is-referenced-by-count":34,"title":["Serum biomarkers associated with baseline clinical severity in young steroid-na\u00efve Duchenne muscular dystrophy boys"],"prefix":"10.1093","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4120-2015","authenticated-orcid":false,"given":"Utkarsh J","family":"Dang","sequence":"first","affiliation":[{"name":"Department of Health Outcomes and Administrative Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton University\u2014SUNY, Binghamton, NY 13902, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Ziemba","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Watson School of Engineering, Binghamton University\u2014SUNY, Binghamton, NY 13902, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula R","family":"Clemens","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA"},{"name":"Department of Veteran Affairs Medical Center, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yetrib","family":"Hathout","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton University\u2014SUNY, Binghamton, NY 13902, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie S","family":"Conklin","sequence":"additional","affiliation":[{"name":"ReveraGen BioPharma, Rockville, MD 20850, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"CINRG Vamorolone 002\/003 Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric P","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton University\u2014SUNY, Binghamton, NY 13902, USA"},{"name":"ReveraGen BioPharma, Rockville, MD 20850, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,6,27]]},"reference":[{"key":"2020090402222431900_ref1","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/0092-8674(87)90579-4","article-title":"Dystrophin: the protein product of the Duchenne muscular dystrophy locus","volume":"51","author":"Hoffman","year":"1987","journal-title":"Cell"},{"key":"2020090402222431900_ref2","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1083\/jcb.201402079","article-title":"Asynchronous remodeling is a driver of failed regeneration in Duchenne muscular dystrophy","volume":"207","author":"Dadgar","year":"2014","journal-title":"J. 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