{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T18:08:07Z","timestamp":1792260487797,"version":"4.4.0"},"reference-count":24,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T00:00:00Z","timestamp":1758931200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T00:00:00Z","timestamp":1758931200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The aim was to evaluate the safety, tolerability, pharmacokinetics, and potential clinical efficacy of AZP2006, an oral pleiotropic drug modulating progranulin levels, in patients with progressive supranuclear palsy (PSP), a rare tauopathy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A randomized, double\u2010blind, placebo\u2010controlled, parallel\u2010group trial was conducted at three sites in France. Eligible participants (age 40\u201380\u2009years, diagnosed with probable or possible PSP) were randomized to receive AZP2006 (60 mg once per day [QD] or 80\/50 mg QD [80 mg for 10\u2009days followed by 50 mg]) or placebo for 12\u2009weeks. Assessments included safety, pharmacokinetics (plasma and whole blood), pharmacodynamics (cerebrospinal fluid and plasma biomarkers), and exploratory clinical efficacy (PSP rating scale, clinical global impression, and activities of daily living). Approximately 2\u2009years post\u2010trial, an open\u2010label extension (OLE) enrolled 15 patients who received active treatment (AZP2006) for 6 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Forty\u2010one patients were screened, 36 randomized, and 34 completed the study. AZP2006 demonstrated acceptable tolerability and safety with no treatment\u2010related serious adverse events. Pharmacokinetic analysis confirmed rapid absorption, a long half\u2010life (60 mg: 764.3 hours; 80\/50 mg: 684.7 hours), and steady\u2010state by day 45 (60 mg) and day 28 (80\/50 mg). Biomarker analyses indicated blood\u2013brain barrier crossing, target engagement, and stabilized progranulin levels. Trends in efficacy favored slower disease progression in AZP2006 groups. The OLE demonstrated a slowed progression of the disease and revealed no notable safety concerns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      AZP2006 was well\u2010tolerated and demonstrated favorable trends in biomarker and clinical outcomes. These preliminary signals support further investigation to determine whether a meaningful clinical benefit can be achieved in PSP with AZP2006. \u00a9 2025 The Author(s).\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.70049","type":"journal-article","created":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T10:15:15Z","timestamp":1758968115000},"page":"2700-2709","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<scp>AZP2006<\/scp>\n                    in Progressive Supranuclear Palsy: Outcomes from a Phase 2a Multicenter, Randomized Trial, and Open\u2010Label Extension on Safety, Biomarkers, and Disease Progression"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7325-0199","authenticated-orcid":false,"given":"Jean\u2010Christophe","family":"Corvol","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9, Assistance Publique H\u00f4pitaux de Paris, Paris Brain Institute, ICM, Inserm, CNRS Department of Neurology, CIC Neurosciences, H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mickael Alexandre","family":"Obadia","sequence":"additional","affiliation":[{"name":"Hospital Foundation Adolphe de Rothschild Neurology Federation, Parkinson Unit  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Moreau","sequence":"additional","affiliation":[{"name":"Lille University. Inserm 1172 Department of Neurology, CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise\u2010Laure","family":"Mariani","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Assistance Publique H\u00f4pitaux de Paris, Paris Brain Institute, ICM, Inserm, CNRS Department of Neurology, CIC Neurosciences, H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Philippe","family":"Brandel","sequence":"additional","affiliation":[{"name":"Hospital Foundation Adolphe de Rothschild Neurology Federation, Parkinson Unit  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Devos","sequence":"additional","affiliation":[{"name":"Lille University. Inserm 1172 Department of Neurology, CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Sambin","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Assistance Publique H\u00f4pitaux de Paris, Paris Brain Institute, ICM, Inserm, CNRS Department of Neurology, CIC Neurosciences, H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Carri\u00e8re","sequence":"additional","affiliation":[{"name":"Lille University. Inserm 1172 Department of Neurology, CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7587-6187","authenticated-orcid":false,"given":"G\u00fcnter","family":"H\u00f6glinger","sequence":"additional","affiliation":[{"name":"Department of Neurology LMU University Hospital, Ludwig\u2010Maximilians\u2010Universit\u00e4t (LMU), German Center for Neurodegenerative Diseases (DZNE), Cluster for Systems Neurology (SyNergy)  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Lebouteux","sequence":"additional","affiliation":[{"name":"Hospital Foundation Adolphe de Rothschild Neurology Federation, Parkinson Unit  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graziella","family":"Mangone","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Assistance Publique H\u00f4pitaux de Paris, Paris Brain Institute, ICM, Inserm, CNRS Department of Neurology, CIC Neurosciences, H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noelle","family":"Callizot","sequence":"additional","affiliation":[{"name":"Alzprotect  Loos France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lien","family":"Blondel","sequence":"additional","affiliation":[{"name":"Alzprotect  Loos France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Defert","sequence":"additional","affiliation":[{"name":"Alzprotect  Loos France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Estrella","sequence":"additional","affiliation":[{"name":"Alzprotect  Loos France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artin","family":"Karapet","sequence":"additional","affiliation":[{"name":"Alzprotect  Loos France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0184-1990","authenticated-orcid":false,"given":"Philippe","family":"Verwaerde","sequence":"additional","affiliation":[{"name":"Alzprotect  Loos France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Defebvre","sequence":"additional","affiliation":[{"name":"Lille University. 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