{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:24:44Z","timestamp":1789982684073,"version":"4.0.1"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,4,11]],"date-time":"2017-04-11T00:00:00Z","timestamp":1491868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007013","name":"F. Hoffmann-La Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Recent advances in understanding Spinal Muscular Atrophy (<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content>) etiopathogenesis prompted development of potent intervention strategies and raised need for sensitive outcome measures capable of assessing disease progression and response to treatment. Several biomarkers have been proposed; nevertheless, no general consensus has been reached on the most feasible ones. We observed a wide range of measures over 1\u00a0year to assess their ability to monitor the disease status and progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>18 <jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> patients and 19 healthy volunteers (<jats:styled-content style=\"fixed-case\">HV<\/jats:styled-content>) were followed in this 52\u2010weeks observational study. Quantitative\u2010<jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">qMRI<\/jats:styled-content>) of both thighs and clinical evaluation of motor function was performed at baseline, 6, 9 and 12\u00a0months follow\u2010up. Blood samples were taken in patients for molecular characterization at screening, 9 and 12\u00a0month follow\u2010up. Progression, responsiveness and reliability of collected indices were quantified. Correlation analysis was performed to test for potential associations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">QMRI<\/jats:styled-content> indices, clinical scales and molecular measures showed high to excellent reliability. Significant differences were found between <jats:styled-content style=\"fixed-case\">qMRI<\/jats:styled-content> of <jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> patients and <jats:styled-content style=\"fixed-case\">HV<\/jats:styled-content>. Significant associations were revealed between multiple <jats:styled-content style=\"fixed-case\">qMRI<\/jats:styled-content> measures and functional clinical scales. None of the <jats:styled-content style=\"fixed-case\">qMRI<\/jats:styled-content>, clinical, or molecular measures was able to detect significant disease progression over 1\u00a0year.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>We probed a variety of quantitative measures for <jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> in a slowly\u2010progressing disease population over 1\u00a0year. The presented measures demonstrated potential to provide a closer link to underlying disease biology as compared to conventional functional scales. The proposed biomarker framework can guide implementation of more sensitive endpoints in future clinical trials and prove their utility in search for novel disease\u2010modifying therapies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.406","type":"journal-article","created":{"date-parts":[[2017,4,11]],"date-time":"2017-04-11T14:11:24Z","timestamp":1491919884000},"page":"292-304","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Longitudinal characterization of biomarkers for spinal muscular atrophy"],"prefix":"10.1002","volume":"4","author":[{"given":"Ulrike","family":"Bonati","sequence":"first","affiliation":[{"name":"Division of Neuropediatrics University of Basel Children's Hospital Spitalstrasse 33 4056 Basel Switzerland"},{"name":"Department of Neurology University of Basel Hospital Petersgraben 4 4031 Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0160tefan","family":"Holiga","sequence":"additional","affiliation":[{"name":"Roche Pharma and Early Development Neuroscience, Ophthalmology and Rare Diseases Roche Innovation Center Basel F. Hoffmann\u2010La Roche Ltd Grenzacherstrasse 124 4070 Basel Switzerland"},{"name":"Max Planck Institute for Human Cognitive and Brain Sciences Stephanstr. 1A 04103 Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Hellbach","sequence":"additional","affiliation":[{"name":"Roche Pharma and Early Development Neuroscience, Ophthalmology and Rare Diseases Roche Innovation Center Basel F. Hoffmann\u2010La Roche Ltd Grenzacherstrasse 124 4070 Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Risterucci","sequence":"additional","affiliation":[{"name":"Roche Pharma and Early Development Neuroscience, Ophthalmology and Rare Diseases Roche Innovation Center Basel F. Hoffmann\u2010La Roche Ltd Grenzacherstrasse 124 4070 Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Bergauer","sequence":"additional","affiliation":[{"name":"Roche Pharma and Early Development Neuroscience, Ophthalmology and Rare Diseases Roche Innovation Center Basel F. Hoffmann\u2010La Roche Ltd Grenzacherstrasse 124 4070 Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wakana","family":"Tang","sequence":"additional","affiliation":[{"name":"Roche Molecular Diagnostics Research Genomics &amp; Oncology Roche Molecular Systems Inc. 4300 Hacienda Dr Pleasanton 94588 California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Hafner","sequence":"additional","affiliation":[{"name":"Division of Neuropediatrics University of Basel Children's Hospital Spitalstrasse 33 4056 Basel Switzerland"},{"name":"Department of Neurology University of Basel Hospital Petersgraben 4 4031 Basel Switzerland"},{"name":"University Clinics of Internal Medicine Kantonsspital Baselland Bruderholz 4101 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Thoeni","sequence":"additional","affiliation":[{"name":"MIAC AG c\/o University of Basel Hospital Mittlere\u2010Strasse 83 4031 Basel Switzerland"},{"name":"Department of Radiology University of Basel Hospital Petersgraben 4 4031 Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Bieri","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Basel Hospital Petersgraben 4 4031 Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Gerlach","sequence":"additional","affiliation":[{"name":"Roche Pharma and Early Development Neuroscience, Ophthalmology and Rare Diseases Roche Innovation Center Basel F. Hoffmann\u2010La Roche Ltd Grenzacherstrasse 124 4070 Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Marquet","sequence":"additional","affiliation":[{"name":"Roche Pharma and Early Development Neuroscience, Ophthalmology and Rare Diseases Roche Innovation Center Basel F. Hoffmann\u2010La Roche Ltd Grenzacherstrasse 124 4070 Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Khwaja","sequence":"additional","affiliation":[{"name":"Roche Pharma and Early Development Neuroscience, Ophthalmology and Rare Diseases Roche Innovation Center Basel F. Hoffmann\u2010La Roche Ltd Grenzacherstrasse 124 4070 Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Sambataro","sequence":"additional","affiliation":[{"name":"Roche Pharma and Early Development Neuroscience, Ophthalmology and Rare Diseases Roche Innovation Center Basel F. Hoffmann\u2010La Roche Ltd Grenzacherstrasse 124 4070 Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Bertolino","sequence":"additional","affiliation":[{"name":"Roche Pharma and Early Development Neuroscience, Ophthalmology and Rare Diseases Roche Innovation Center Basel F. Hoffmann\u2010La Roche Ltd Grenzacherstrasse 124 4070 Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juergen","family":"Dukart","sequence":"additional","affiliation":[{"name":"Roche Pharma and Early Development Neuroscience, Ophthalmology and Rare Diseases Roche Innovation Center Basel F. Hoffmann\u2010La Roche Ltd Grenzacherstrasse 124 4070 Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne","family":"Fischmann","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Basel Hospital Petersgraben 4 4031 Basel Switzerland"},{"name":"Hirslanden Klinik St. Anna St. Anna\u2010Strasse 32 6006 Luzern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Fischer","sequence":"additional","affiliation":[{"name":"Division of Neuropediatrics University of Basel Children's Hospital Spitalstrasse 33 4056 Basel Switzerland"},{"name":"Department of Neurology University of Basel Hospital Petersgraben 4 4031 Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Czech","sequence":"additional","affiliation":[{"name":"Roche Pharma and Early Development Neuroscience, Ophthalmology and Rare Diseases Roche Innovation Center Basel F. Hoffmann\u2010La Roche Ltd Grenzacherstrasse 124 4070 Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,4,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60921-6"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70061-3"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/joa.12083"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1250127"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.14.63"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2015.77"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.2014.896335"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.15.101"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002445"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.23937"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0139950"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.283"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms12010024"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033572"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-010-1799-2"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2012.06.005"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)00242-2"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2015.05.006"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02015357"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.20804"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2012.05.015"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.23998"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.10101108"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.22842"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-011-5937-9"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073810380457"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073811405053"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2012.05.014"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.24220"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.153.1.6089263"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2006.01.015"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.22431"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2013.01.014"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2005.03.004"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181d3e308"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1037\/0033-2909.86.2.420"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471445428"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-4356(99)00206-1"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.319"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002464"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0070993"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2010.373"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2015.10.006"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.3233\/JND-160145"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Facn3.406","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.406","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T23:18:00Z","timestamp":1696547880000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.406"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,11]]},"references-count":44,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,5]]}},"alternative-id":["10.1002\/acn3.406"],"URL":"https:\/\/doi.org\/10.1002\/acn3.406","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,11]]},"assertion":[{"value":"2017-02-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-03-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-04-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}