{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:41:45Z","timestamp":1790779305759,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,5,16]],"date-time":"2019-05-16T00:00:00Z","timestamp":1557964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Limb girdle muscular dystrophy type R9 (<jats:styled-content style=\"fixed-case\">LGMD<\/jats:styled-content> R9) is an autosomal recessive muscle disease for which there is currently no causative treatment. The development of putative therapies requires sensitive outcome measures for clinical trials in this slowly progressing condition. This study extends functional assessments and <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content> muscle fat fraction measurements in an <jats:styled-content style=\"fixed-case\">LGMD<\/jats:styled-content> R9 cohort across 6\u00a0years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty\u2010three participants with <jats:styled-content style=\"fixed-case\">LGMD<\/jats:styled-content> R9, previously assessed over a 1\u2010year period, were re\u2010enrolled at 6\u00a0years. Standardized functional assessments were performed including: myometry, timed tests, and spirometry testing. Quantitative <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content> was used to measure fat fraction in lower limb skeletal muscle groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At 6\u00a0years, all 14 muscle groups assessed demonstrated significant increases in fat fraction, compared to eight groups in the 1\u2010year follow\u2010up study. In direct contrast to the 1\u2010year follow\u2010up, the 6\u2010min walk test, 10\u2010m walk or run, timed up and go, stair ascend, stair descend and chair rise demonstrated significant decline. Among the functional tests, only <jats:styled-content style=\"fixed-case\">FVC<\/jats:styled-content> significantly declined over both the 1\u2010 and 6\u2010year studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>These results further support fat fraction measurements as a primary outcome measure alongside functional assessments. The most appropriate individual muscles are the vastus lateralis, gracilis, sartorius, and gastrocnemii. Using composite groups of lower leg muscles, thigh muscles, or triceps surae, yielded high standardized response means (<jats:styled-content style=\"fixed-case\">SRM<\/jats:styled-content>s). Over 6\u00a0years, quantitative fat fraction assessment demonstrated higher <jats:styled-content style=\"fixed-case\">SRM<\/jats:styled-content> values than seen in functional tests suggesting greater responsiveness to disease progression.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.774","type":"journal-article","created":{"date-parts":[[2019,5,16]],"date-time":"2019-05-16T18:11:55Z","timestamp":1558030315000},"page":"1033-1045","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Natural history of limb girdle muscular dystrophy R9 over 6\u00a0years: searching for trial endpoints"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4244-0541","authenticated-orcid":false,"given":"Alexander P.","family":"Murphy","sequence":"first","affiliation":[{"name":"The John Walton Muscular Dystrophy Research Centre Institute of Genetic Medicine Newcastle University Newcastle Hospitals NHS Foundation Trust Central Parkway Newcastle Upon Tyne United Kingdom NE1 4EP"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper","family":"Morrow","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurosciences MRC Centre for Neuromuscular Diseases UCL Institute of Neurology London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3149-1661","authenticated-orcid":false,"given":"Julia R.","family":"Dahlqvist","sequence":"additional","affiliation":[{"name":"Department of Neurology Copenhagen Neuromuscular Center Rigshospitalet University of Copenhagen Blegdamsvej 9 2100 Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Stojkovic","sequence":"additional","affiliation":[{"name":"Institute of Myology AP6HP, G\u2010H Piti\u00e9\u2010Salp\u00eatri\u00e8re 47\u201083 boulevard de l'h\u00f4pital 75651 Paris Cedex 13 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey A.","family":"Willis","sequence":"additional","affiliation":[{"name":"The Robert Jones and Agnes Hunt Orthopaedic Hospital Oswestry Shropshire United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D. 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