{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:50:31Z","timestamp":1790801431794,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T00:00:00Z","timestamp":1753747200000},"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":["Annals of Neurology"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Exenatide, a glucagon\u2010like peptide\u20101 (GLP\u20101) receptor agonist, has neuroprotective effects in preclinical models of multiple system atrophy (MSA). We investigated these effects in a proof\u2010of\u2010concept clinical trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this single\u2010center, randomized, open label trial, participants with MSA were randomly assigned (1:1) to receive subcutaneous injections of exenatide 2\u2009mg weekly for 48\u2009weeks, or as controls, followed by a 48\u2010week washout period. The primary outcome was the Unified Multiple System Atrophy Rating Scale (UMSARS) parts I\u2009+\u2009II combined score at 48\u2009weeks. Objective secondary outcome measures included the numbers of participants losing ambulation; scoring \u2265\u20093 on UMSARS part I items for falls, speech, swallowing, as well as timed walking and measures of quality of life and cognition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Between September 23, 2020, and May 6, 2022, 50 participants were recruited (25 in each group). At 48\u2009weeks, UMSARS parts I\u2009+\u2009II scores had worsened by 6.1 points (95% confidence interval [CI]\u2009=\u20093.0 to 9.3, SD\u2009=\u20096.9) in the exenatide group and by 13\u20093 points (95% CI\u2009=\u20099.2 to 17.3, SD\u2009=\u20099.4) in the control group, an adjusted mean difference of \u22127.4 points (\u221211.3 to \u22123.6,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0003). There were no statistically significant differences at either 48 or 96\u2009weeks in the secondary outcome measures. Biomarker analysis of neurofilament light chain and cerebral spinal fluid (CSF) alpha\u2010synuclein oligomer load, sensor\u2010derived gait measures, and imaging findings were also similar between groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Exenatide was associated with positive effects on participant\u2010reported symptoms and clinician\u2010rated MSA severity. In contrast, none of the objective comparisons differed according to randomization. Given the open label trial design, the discrepancy between the primary outcome and the objective measures may be explicable as placebo effects\/observer bias. ANN NEUROL 2025;98:991\u20131003<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.70004","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T09:53:57Z","timestamp":1753782837000},"page":"991-1003","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Exenatide Once Weekly in the Treatment of Patients with Multiple System Atrophy"],"prefix":"10.1002","volume":"98","author":[{"given":"Nirosen","family":"Vijiaratnam","sequence":"first","affiliation":[{"name":"Department of Clinical and Movement Neurosciences University College London Queen Square Institute of Neurology  London UK"},{"name":"National Hospital for Neurology and Neurosurgery  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Girges","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences University College London Queen Square Institute of Neurology  London UK"},{"name":"National Hospital for Neurology and Neurosurgery  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Wiegand","sequence":"additional","affiliation":[{"name":"Department of Statistical Science, University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Ismail","sequence":"additional","affiliation":[{"name":"NIHR UCLH Clinical Research Facility  London England UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Lameirinhas","sequence":"additional","affiliation":[{"name":"NIHR UCLH Clinical Research Facility  London England UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Yarnall","sequence":"additional","affiliation":[{"name":"Newcastle NIHR BRC, Translational and Clinical Research Institute Newcastle University, Newcastle Upon Tyne  England UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron","family":"Kirk","sequence":"additional","affiliation":[{"name":"Newcastle NIHR BRC, Translational and Clinical Research Institute Newcastle University, Newcastle Upon Tyne  England UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Del\u2010Din","sequence":"additional","affiliation":[{"name":"Newcastle NIHR BRC, Translational and Clinical Research Institute Newcastle University, Newcastle Upon Tyne  England UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn","family":"Rochester","sequence":"additional","affiliation":[{"name":"Newcastle NIHR BRC, Translational and Clinical Research Institute Newcastle University, Newcastle Upon Tyne  England UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Kobylecki","sequence":"additional","affiliation":[{"name":"Manchester Centre for Clinical Neurosciences, Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science Centre University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth","family":"Ambler","sequence":"additional","affiliation":[{"name":"Department of Statistical Science, University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7828-3122","authenticated-orcid":false,"given":"Simon","family":"Skene","sequence":"additional","affiliation":[{"name":"Surrey Clinical Trials Unit University of Surrey. 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