{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T12:37:30Z","timestamp":1789043850396,"version":"build-2803163510"},"update-to":[{"DOI":"10.12688\/wellcomeopenres.17398.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T00:00:00Z","timestamp":1660694400000}}],"reference-count":60,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T00:00:00Z","timestamp":1660694400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015408","name":"Industrial Support","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015408","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["101550"],"award-info":[{"award-number":["101550"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns3:p>\n                    <ns3:bold>Background:<\/ns3:bold>\n                    Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease caused by mutations in the dystrophin gene. Due to their phenotypic similarity to human patients, large animal models are invaluable tools for pre-clinical trials. The DE50-MD dog is a relatively new model of DMD, and carries a therapeutically-tractable mutation lying within the hotspot for human patients, making it especially valuable. Prior to conducting therapeutic trials using this novel animal model, it is essential to establish a panel of viable biomarkers.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Methods:<\/ns3:bold>\n                    We evaluated a panel of blood-borne biomarkers of musculoskeletal disease in the DE50-MD dog. Venous blood samples were obtained monthly throughout an 18-month study period in DE50-MD (N=18) and wild-type (WT) control (N=14) dogs. A panel of potential plasma\/serum biomarkers of DMD was measured and their theoretical utility in future clinical trials determined using sample size calculations.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Results:<\/ns3:bold>\n                    Compared to WT dogs, DE50-MD dogs had substantially higher circulating creatine kinase (CK) activities, myomesin-3 (MYOM3), and the dystromiRs miR-1, miR-133a and miR-206, but significantly lower serum myostatin concentrations. An age-associated pattern, similar to that observed in DMD patients, was seen for CK and MYOM3. Sample size calculations suggested that low cohort sizes (N\u22643) could be used to detect up to a 50% improvement\u00a0in DE50-MD results towards WT levels for each biomarker or a combination thereof (via principal component analysis); as few as N=3 animals should enable detection of a 25% improvement using a combined biomarker approach (alpha 0.05, power 0.8).\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Conclusions:<\/ns3:bold>\n                    We have established a panel of blood-borne biomarkers that could be used to monitor musculoskeletal disease or response to a therapeutic intervention in the DE50-MD dog using low numbers of animals. The blood biomarker profile closely mimics that of DMD patients, supporting the hypothesis that this DMD model would be suitable for use in pre-clinical trials.\n                  <\/ns3:p>","DOI":"10.12688\/wellcomeopenres.17398.2","type":"journal-article","created":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T11:05:06Z","timestamp":1660734306000},"page":"354","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Longitudinal assessment of blood-borne musculoskeletal disease biomarkers in the DE50-MD dog model of Duchenne muscular dystrophy"],"prefix":"10.12688","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1614-504X","authenticated-orcid":false,"given":"Dominique O.","family":"Riddell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2283-2118","authenticated-orcid":false,"given":"John C. 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M.","family":"Harron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1425-6344","authenticated-orcid":false,"given":"Dominic J.","family":"Wells","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4344-6438","authenticated-orcid":false,"given":"Richard J.","family":"Piercy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2022,8,17]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"304-13","DOI":"10.1002\/ana.23528","article-title":"Evidence-based path to newborn screening for Duchenne muscular dystrophy.","volume":"71","author":"J Mendell","year":"2012","journal-title":"Ann 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