{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:22:40Z","timestamp":1790947360964,"version":"4.1.0"},"reference-count":28,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T00:00:00Z","timestamp":1644883200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPD"],"published-print":{"date-parts":[[2022,2,15]]},"abstract":"<jats:p>Background: Glucocerebrosidase gene (GBA) mutations influence risk and prognosis of Parkinson\u2019s disease (PD), possibly through accumulation of glycosphingolipids, including glucosylceramide (GL-1). Venglustat is a novel, brain penetrant glucosylceramide synthase inhibitor. Objective: Evaluate venglustat pharmacology, safety, and tolerability in patients with PD and GBA mutations (GBA-PD). Methods: Part 1 of the phase 2 MOVES-PD trial (NCT02906020) was a randomized, double-blinded, placebo-controlled, dose-escalation study performed in six countries. Eligible participants included Japanese and non-Japanese patients aged 18\u201380 years with PD diagnosis and heterozygous GBA mutation. Participants were randomized to three doses of once-daily oral venglustat or placebo and were followed up to 36 weeks (Japanese participants: 52 weeks). Primary endpoint was venglustat safety and tolerability versus placebo. Secondary and exploratory endpoints included venglustat pharmacokinetics and pharmacodynamics. Results: Participants (N\u200a=\u200a29) received venglustat (Japanese, n\u200a=\u200a9; non-Japanese, n\u200a=\u200a13) or placebo (n\u200a=\u200a3; n\u200a=\u200a4). Eight (89%) Japanese and 12 (92%) non-Japanese venglustat-treated participants experienced at least one adverse event (AE) versus two (67%) and four (100%) participants from the respective placebo groups. Most AEs were mild or moderate; no serious AEs or deaths occurred. Two venglustat-treated non-Japanese participants discontinued due to AEs (confusional state and panic attack). Over 4 weeks, venglustat exposure in plasma and cerebrospinal fluid (CSF) increased, and GL-1 levels in plasma and CSF decreased, both in a dose-dependent manner. At the highest dose, CSF GL-1 decreased by 72.0% in Japanese and 74.3% in non-Japanese participants. Conclusion: Venglustat showed favorable safety and tolerability in MOVES-PD Part 1 and target engagement was achieved in CSF.<\/jats:p>","DOI":"10.3233\/jpd-212714","type":"journal-article","created":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T12:07:21Z","timestamp":1639138041000},"page":"557-570","source":"Crossref","is-referenced-by-count":55,"title":["Safety, Pharmacokinetics, and Pharmacodynamics of Oral Venglustat in Patients with Parkinson\u2019s Disease and a GBA Mutation: Results from Part 1 of the Randomized, Double-Blinded, Placebo-Controlled MOVES-PD Trial"],"prefix":"10.1177","volume":"12","author":[{"given":"M. Judith","family":"Peterschmitt","sequence":"first","affiliation":[{"name":"Sanofi, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the MOVES-PD Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidemoto","family":"Saiki","sequence":"additional","affiliation":[{"name":"Kitano Hospital, The Tazuke Kofukai Medical Research Institute, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Hatano","sequence":"additional","affiliation":[{"name":"Juntendo University, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Gasser","sequence":"additional","affiliation":[{"name":"Neurologische Universit\u00e4tsklinik, T\u00fcbingen, Germany; German Center for Neurodegenerative Diseases (DZNE), T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart H.","family":"Isaacson","sequence":"additional","affiliation":[{"name":"Parkinson\u2019s Disease and Movement Disorders Center, Boca Raton, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastiaan J.M.","family":"Gaemers","sequence":"additional","affiliation":[{"name":"Sanofi Genzyme, Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Minini","sequence":"additional","affiliation":[{"name":"Sanofi, Chilly-Mazarin, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Saubadu","sequence":"additional","affiliation":[{"name":"Sanofi, Chilly-Mazarin, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyoti","family":"Sharma","sequence":"additional","affiliation":[{"name":"Sanofi, Bridgewater, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Walbillic","sequence":"additional","affiliation":[{"name":"Sanofi, Chilly-Mazarin, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy N.","family":"Alcalay","sequence":"additional","affiliation":[{"name":"Department of Neurology and the Taub Institute, Columbia University Medical Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Cutter","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham, School of Public Health, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobutaka","family":"Hattori","sequence":"additional","affiliation":[{"name":"Juntendo University, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcnter U.","family":"H\u00f6glinger","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), Munich, and Department of Neurology, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany"},{"name":"Department of Neurology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Marek","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Disorders, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony H.V.","family":"Schapira","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens R.","family":"Scherzer","sequence":"additional","affiliation":[{"name":"Harvard Medical School and Brigham & Women\u2019s Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Simuni","sequence":"additional","affiliation":[{"name":"Northwestern University, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nir","family":"Giladi","sequence":"additional","affiliation":[{"name":"Neurological Institute, Tel Aviv Medical Center, Sackler School of Medicine, Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio Pablo","family":"Sardi","sequence":"additional","affiliation":[{"name":"Sanofi, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya Z.","family":"Fischer","sequence":"additional","affiliation":[{"name":"Sanofi, Cambridge, MA, 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