{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T00:54:50Z","timestamp":1794272090664,"version":"4.9.0"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"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":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Variants in the\n                      <jats:italic>GBA1<\/jats:italic>\n                      gene can increase the risk of Parkinson's disease (PD) by reducing glucocerebrosidase (GCase) activity, disrupting lysosomal and mitochondrial function, and increasing alpha\u2010synuclein aggregation. The molecule GT\u201002287 prevents misfolding of GCase and ameliorates downstream pathway abnormalities.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of GT\u201002287.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The safety, tolerability, and plasma pharmacokinetics of single and multiple oral doses were evaluated in 73 healthy volunteers, and GT\u201002287 levels in cerebrospinal fluid (CSF) and GCase activity in blood were measured.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All dose levels tested were safe and generally well\u2010tolerated. No serious or severe adverse events occurred. The most common events were nausea and headache. Plasma and CSF exposures were within the projected therapeutic range, and GCase activity increased after GT\u201002287 administration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>GT\u201002287 was safe and well\u2010tolerated in healthy volunteers. Plasma and CSF levels were consistent with levels in rodents that modulate PD biology. \u00a9 2025 International Parkinson and Movement Disorder Society.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.70111","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T07:20:25Z","timestamp":1762413625000},"page":"522-527","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Glucocerebrosidase Target Engagement and Therapeutic Plasma and Cerebrospinal Fluid Levels After\n                    <scp>GT<\/scp>\n                    \u201002287 Administration in Healthy Volunteers"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3426-125X","authenticated-orcid":false,"given":"Raffaella","family":"Pozzi","sequence":"first","affiliation":[{"name":"Gain Therapeutics  Lugano Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"De Sciscio","sequence":"additional","affiliation":[{"name":"CMAX Clinical Research  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1972-7701","authenticated-orcid":false,"given":"Manuela","family":"Bosetti","sequence":"additional","affiliation":[{"name":"Gain Therapeutics  Lugano Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Cano\u2010Crespo","sequence":"additional","affiliation":[{"name":"Gain Therapeutics Sucursal en Espa\u00f1a  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Taylor","sequence":"additional","affiliation":[{"name":"Gain Therapeutics  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terenzio","family":"Ignoni","sequence":"additional","affiliation":[{"name":"Gain Therapeutics  Lugano Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3772-4865","authenticated-orcid":false,"given":"Jonas","family":"Hannestad","sequence":"additional","affiliation":[{"name":"Gain Therapeutics  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.1783"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30295-3"},{"key":"e_1_2_9_4_1","unstructured":"World Health Organization (WHO).Parkinson disease [Online Fact Sheet];2023. Accessed March 11 2025.https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/parkinson-disease."},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.11.007"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26071"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0115747"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2019.12.011"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp044"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0901281"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2014_315"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318225ab77"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0167749"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2015.08.027"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24777"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2017-317348"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2018.05.009"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-024-01775-4"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11081261"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26094392"},{"key":"e_1_2_9_21_1","unstructured":"P\u00e9rez\u2010CarmonaN Guzm\u00e1nB Garc\u00eda\u2010CollazoA TaylorJ.GT\u201002287 a clinical stage GCase regulator improves mitochondrial function and provides a neuroprotective effect in GBA1\u2010Parkinson's disease models. Program No. PSTR063.07. Society for Neuroscience; Chicago IL: 2024 Neuroscience Meeting Planner;2024."},{"key":"e_1_2_9_22_1","unstructured":"TaylorJ Guzm\u00e1nB P\u00e9rez\u2010CarmonaN Garc\u00eda\u2010CollazoA.Clinical stage allosteric glucocerebrosidase modulator GT\u201002287 shows disease modifying potential in preclinical models of both GBA1 and idiopathic Parkinson's disease (ID 836). AD\/PD 2025 International Conference on Alzheimer's and Parkinson's Diseases and Related Neurological Disorders; Vienna Austria;2025."},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00205-3"},{"key":"e_1_2_9_24_1","unstructured":"ClinicalTrials.gov.Efficacy Safety Tolerability Pharmacodynamics and Pharmacokinetics of BIA 28\u20136156 in GBA\u2010PD (ACTIVATE). ClinicalTrials.gov Identifier: NCT05819359; Bethesda MD: National Library of Medicine (US);2024. Accessed March 24 2025.https:\/\/clinicaltrials.gov\/study\/NCT05819359."},{"key":"e_1_2_9_25_1","volume-title":"Vanqua Bio Announces Positive Interim Results from Phase 1 Clinical Trial of VQ\u2010101, an Orally Administered, Brain\u2010Penetrant, Allosteric Activator of GCase for the Treatment of GBA\u2010Parkinson's and Related Disorders [Press Release]","year":"2024"},{"key":"e_1_2_9_26_1","unstructured":"ClinicalTrials.gov.Ambroxol to Slow Progression in Parkinson Disease (ASPro\u2010PD). ClinicalTrials.gov Identifier: NCT05778617. Bethesda MD: National Library of Medicine (US);2024. Accessed March 24 2025.https:\/\/clinicaltrials.gov\/study\/NCT05778617."},{"key":"e_1_2_9_27_1","unstructured":"ClinicalTrials.gov.GRoningen Early\u2010PD Ambroxol Treatment (GREAT). ClinicalTrials.gov Identifier: NCT05830396. Bethesda MD: National Library of Medicine (US);2023. Accessed March 24 2025.https:\/\/clinicaltrials.gov\/study\/NCT05830396."},{"key":"e_1_2_9_28_1","unstructured":"ClinicalTrials.gov [Internet].Phase 1\/ 2a Clinical Trial of PR001 (LY3884961) in Patients With Parkinson's Disease With at Least One GBA1 Mutation (PROPEL). ClinicalTrials.gov Identifier: NCT04127578. Bethesda MD: National Library of Medicine (US);2025. Accessed March 24 2025.https:\/\/clinicaltrials.gov\/study\/NCT04127578."},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37454-4"},{"key":"e_1_2_9_30_1","unstructured":"ClinicalTrials.gov.Safety Tolerability Pharmacokinetics and Pharmacodynamics of GT\u201002287 in Parkinson's Disease. ClinicalTrials.gov Identifier: NCT06732180. Bethesda MD: National Library of Medicine (US);2025. Accessed March 24 2025.https:\/\/clinicaltrials.gov\/study\/NCT06732180."}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.70111","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mds.70111","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.70111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T15:27:26Z","timestamp":1772983646000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.70111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,5]]},"references-count":29,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/mds.70111"],"URL":"https:\/\/doi.org\/10.1002\/mds.70111","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,5]]},"assertion":[{"value":"2025-08-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}