{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T05:14:09Z","timestamp":1792818849915,"version":"4.5.0"},"reference-count":33,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000900","name":"California Institute for Regenerative Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000900","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>Glial cell line\u2013derived neurotrophic factor (GDNF) is required for development and survival of dopaminergic neurons. A previous trial evaluating lower\u2010dose adeno\u2010associated virus serotype 2\u2013GDNF (AAV2\u2010GDNF) bilateral intraputaminal infusion in participants with advanced Parkinson's disease (PD) achieved 26% mean putaminal coverage and was associated with stable motor features with no unexpected adverse events (AEs) over 60\u2009months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We assessed safety and preliminary clinical outcomes of optimized bilateral intraputaminal infusion of a single, higher dose of AAV2\u2010GDNF (product code AB\u20101005) for PD after 18\u2009months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This phase 1b single\u2010arm, open\u2010label clinical trial enrolled participants with mild (Movement Disorder Society\u2013revised Unified Parkinson's Disease Rating Scale [MDS\u2010UPDRS] Part III <jats:italic>off<\/jats:italic> score\u2009\u2264\u200932) and moderate (MDS\u2010UPDRS Part III <jats:italic>off<\/jats:italic> score of 33\u201360) PD. The primary outcome was safety. Clinical outcomes were assessed using PD\u2010specific clinical measures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eleven participants were enrolled (n\u2009=\u20096 mild; n\u2009=\u20095 moderate). Mean (\u00b1SE) putaminal coverage of AAV2\u2010GDNF was 63% (\u00b12%). All participants experienced treatment\u2010emergent AEs (63 events); most were transient and perioperative. Six serious AEs in three participants were unrelated to AAV2\u2010GDNF. At 18\u2009months posttreatment, the mild cohort exhibited numerically stable MDS\u2010UPDRS, motor diary, Unified Dyskinesia Rating Scale (UDysRS) scores, and levodopa equivalent daily dose (LEDD). The moderate cohort demonstrated numerical improvements in mean (\u00b1SE) MDS\u2010UPDRS Part III <jats:italic>off<\/jats:italic> scores (\u221220.4 [\u00b14.5]), motor diary <jats:italic>off<\/jats:italic> time (\u22121.7 [\u00b11.1] hours), and UDysRS scores (\u22122.2 [\u00b11.9]) and reduced LEDD (\u2212257.6 [\u00b1162.2] mg).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Bilateral intraputaminal AAV2\u2010GDNF gene therapy was well tolerated and associated with numerical stability (mild cohort) and improvement (moderate cohort) in clinical assessments at 18\u2009months posttreatment. \u00a9 2025 AskBio Inc and 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.30193","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T02:31:05Z","timestamp":1747794665000},"page":"1297-1306","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Intraputaminal Delivery of Adeno\u2010Associated Virus Serotype 2<b>\u2013<\/b>Glial Cell Line\u2013Derived Neurotrophic Factor in Mild or Moderate Parkinson's Disease"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8912-3159","authenticated-orcid":false,"given":"Amber D.","family":"Van Laar","sequence":"first","affiliation":[{"name":"AskBio, Inc.  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4166-9432","authenticated-orcid":false,"given":"Chadwick W.","family":"Christine","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4631-7551","authenticated-orcid":false,"given":"Nicol\u00e1s","family":"Phielipp","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California Irvine  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul S.","family":"Larson","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery University of Arizona  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Bradley","family":"Elder","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery The Ohio State University Wexner Medical Center  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5587-726X","authenticated-orcid":false,"given":"Aristide","family":"Merola","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery The Ohio State University Wexner Medical Center  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waldy","family":"San Sebastian","sequence":"additional","affiliation":[{"name":"AskBio, Inc.  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo S.","family":"Fiandaca","sequence":"additional","affiliation":[{"name":"AskBio, Inc.  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian P.","family":"Kells","sequence":"additional","affiliation":[{"name":"AskBio, Inc.  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Wisniewski","sequence":"additional","affiliation":[{"name":"AskBio, Inc.  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krystof S.","family":"Bankiewicz","sequence":"additional","affiliation":[{"name":"AskBio, Inc.  Durham North Carolina USA"},{"name":"Department of Neurological Surgery The Ohio State University Wexner Medical Center  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2013.281"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/1566523220999200817164051"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.151179"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2015.11.006"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2136"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz023"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20737"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2011.11"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.6.2076"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27724"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2022.08.003"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(02)00022-2"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2008.201"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.55.3.181"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2014.10.026"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2020-322904"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3171\/2019.4.JNS19826"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25450"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70254-4"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00701-023-05799-w"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-202004"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0178984"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-191576"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24436"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(11)70039-4"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.12632"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2009.295"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20914"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X20666211223122800"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prdoa.2022.100140"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29518"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0942-10.2010"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.13687"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.30193","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T09:51:19Z","timestamp":1760953879000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.30193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,20]]},"references-count":33,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1002\/mds.30193"],"URL":"https:\/\/doi.org\/10.1002\/mds.30193","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,20]]},"assertion":[{"value":"2024-09-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}