{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:26:32Z","timestamp":1793413592286,"version":"4.5.0"},"reference-count":30,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T00:00:00Z","timestamp":1744934400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003136","name":"Edmond J. Safra Philanthropic Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003136","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>There are currently no disease\u2010modifying therapies (DMTs) registered for Parkinson's disease (PD). The Edmond J. Safra Accelerating Clinical Trials in Parkinson Disease (EJS ACT\u2010PD) initiative will expedite clinical assessment of putative DMTs through a multi\u2010arm multistage (MAMS) trial, testing several treatments against a common placebo arm and replacing unsuccessful therapies early.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The objective of this study was to describe the treatment selection process for the EJS ACT\u2010PD clinical trial platform.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A Treatment Selection Working Group (TSWG) identified compounds using complementary strategies, such as literature search, related initiatives (Cure Parkinson's International Linked Clinical Trials [iLCT] initiative), and expert suggestions. Compounds were classified into five mechanistic subgroups (mitochondrial, lysosomal, protein, inflammation, \u201cother\u201d). \u201cGo\/No\u2010Go\u201d criteria and a scoring system covering preclinical, pharmacological, and clinical evidence were devised. Experts scored the candidates for quantitative rankings. Dossiers adapted from iLCT documents were produced for the top\u2010ranked compounds and in turn prioritized by the TSWG. Practical and logistical considerations from the Steering Committee (SC) guided the final decision. Patient and Public Involvement and Engagement representatives provided feedback throughout the process.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 293 interventions were identified, 52 of which passed the \u201cGo\/No\u2010Go\u201d criteria and were scored. Dossiers of the 14 top\u2010ranked compounds were submitted to the SC. Telmisartan, terazosin, and ursodeoxycholic acid were selected as the initial interventions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Drug selection in DMT PD MAMS trials requires consideration of scientific and practical issues. We present a robust system that can inform similar initiatives. \u00a9 2025 The Author(s). <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.30190","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T08:55:02Z","timestamp":1748336102000},"page":"1307-1317","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Treatment Selection and Prioritization for the <scp>EJS ACT<\/scp>\u2010<scp>PD MAMS<\/scp> Trial Platform"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6809-0127","authenticated-orcid":false,"given":"Cristina","family":"Gonzalez\u2010Robles","sequence":"first","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology University College London  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T.","family":"Dexter","sequence":"additional","affiliation":[{"name":"Parkinson's UK  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3408-5973","authenticated-orcid":false,"given":"Susan","family":"Duty","sequence":"additional","affiliation":[{"name":"Wolfson Sensory, Pain and Regeneration Centre, Institute of Psychiatry, Psychology &amp; Neuroscience King's College London  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romy","family":"Ellis\u2010Doyle","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology University College London  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Gandhi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology University College 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