{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T07:48:49Z","timestamp":1791791329369,"version":"4.3.4"},"reference-count":24,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS003051\u201018"],"award-info":[{"award-number":["NS003051\u201018"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS\u2010003032\u201017"],"award-info":[{"award-number":["NS\u2010003032\u201017"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["X01NS065758\u201001"],"award-info":[{"award-number":["X01NS065758\u201001"]}],"id":[{"id":"10.13039\/100000002","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":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Parkinson's disease (PD) is a progressive neurodegenerative disorder. Neurotrophic therapeutic approaches have been limited in part by incomplete delivery to the putamen. We developed image\u2010guided convection\u2010enhanced delivery with real\u2010time monitoring to improve intraputaminal distribution of neurotrophic gene therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      To evaluate the 5\u2010year safety and tolerability of bilateral putaminal delivery of adeno\u2010associated virus serotype 2 encoding glial cell line\u2010derived neurotrophic factor (\n                      <jats:styled-content style=\"fixed-case\">AAV2<\/jats:styled-content>\n                      \u2010\n                      <jats:styled-content style=\"fixed-case\">GDNF)<\/jats:styled-content>\n                      , and to describe exploratory long\u2010term clinical outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This was a single\u2010center, open\u2010label, phase 1, dose\u2010escalation study in adults with advanced PD. Thirteen participants received bilateral putaminal infusions across three dose cohorts (six low\u2010dose, six medium\u2010dose, one high\u2010dose) and were followed for 5\u2009years. Adverse events, including serious adverse events, were collected, and their relationship to the study agent was determined. Longitudinal clinical outcomes were analyzed with a mixed\u2010effects model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Across follow\u2010up, 562 adverse events were recorded; 45 were considered possibly or probably related to the study drug. The 13 serious adverse events that occurred were not attributed to the study drug. One participant died 45\u2009months after infusion from aspiration pneumonia following cervical spine surgery at an outside institution. The study drug had a mean putaminal coverage of 26%\u2009\u00b1\u200910%. Exploratory clinical measures did not change significantly between baseline and final follow\u2010up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Bilateral putaminal neurotrophic gene therapy delivered with real\u2010time image guidance was well tolerated over 5\u2009years, without protocol\u2010defined stopping events. \u00a9 2026 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. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.70393","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:57:32Z","timestamp":1783346252000},"page":"2399-2407","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Phase 1 Study of Convection\u2010Enhanced Delivery of Intraputaminal\n                    <scp>AAV2<\/scp>\n                    \u2010\n                    <scp>GDNF<\/scp>\n                    in Advanced Parkinson's Disease"],"prefix":"10.1002","volume":"41","author":[{"given":"John D.","family":"Heiss","sequence":"first","affiliation":[{"name":"Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra J.","family":"Ehrlich","sequence":"additional","affiliation":[{"name":"Parkinson's Disease Clinic, National Institute of Neurological Disorders and Stroke National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Codrin","family":"Lungu","sequence":"additional","affiliation":[{"name":"Parkinson's Disease Clinic, National Institute of Neurological Disorders and Stroke National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2408-138X","authenticated-orcid":false,"given":"Joseph Y.","family":"Choi","sequence":"additional","affiliation":[{"name":"Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gretchen","family":"Scott","sequence":"additional","affiliation":[{"name":"Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Dustin","sequence":"additional","affiliation":[{"name":"Parkinson's Disease Clinic, National Institute of Neurological Disorders and Stroke National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dima A.","family":"Hammoud","sequence":"additional","affiliation":[{"name":"Radiology and Imaging Sciences, Clinical Center National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Herscovitch","sequence":"additional","affiliation":[{"name":"Positron Emission Tomography Department, Clinical Center National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell R.","family":"Lonser","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery The Ohio State University College of Medicine  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8575-3578","authenticated-orcid":false,"given":"Kareem A.","family":"Zaghloul","sequence":"additional","affiliation":[{"name":"Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krystof","family":"Bankiewicz","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery The Ohio State University College of Medicine  Columbus Ohio 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