{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T19:51:48Z","timestamp":1790970708341,"version":"4.1.0"},"reference-count":16,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2006,1,20]],"date-time":"2006-01-20T00:00:00Z","timestamp":1137715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2006,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title><jats:styled-content><jats:italic>Objective<\/jats:italic><\/jats:styled-content><\/jats:title><jats:p>Glial cell line\u2013derived neurotrophic factor (GDNF) exerts potent trophic influence on midbrain dopaminergic neurons. This randomized controlled clinical trial was designed to confirm initial clinical benefits observed in a small, open\u2010label trial using intraputamenal (Ipu) infusion of recombinant human GDNF (liatermin).<\/jats:p><\/jats:sec><jats:sec><jats:title><jats:styled-content><jats:italic>Methods<\/jats:italic><\/jats:styled-content><\/jats:title><jats:p>Thirty\u2010four PD patients were randomized 1 to 1 to receive bilateral continuous Ipu infusion of liatermin 15\u03bcg\/putamen\/day or placebo. The primary end point was the change in Unified Parkinson Disease Rating Scale (UPDRS) motor score in the practically defined off condition at 6 months. Secondary end points included other UPDRS scores, motor tests, dyskinesia ratings, patient diaries, and <jats:sup>18<\/jats:sup>F\u2010dopa uptake.<\/jats:p><\/jats:sec><jats:sec><jats:title><jats:styled-content><jats:italic>Results<\/jats:italic><\/jats:styled-content><\/jats:title><jats:p>At 6 months, mean percentage changes in \u201coff\u201d UPDRS motor score were \u221210.0% and \u22124.5% in the liatermin and placebo groups, respectively. This treatment difference was not significant (95% confidence interval, \u221223.0 to 12.0, <jats:italic>p<\/jats:italic> = 0.53). Secondary end point results were similar between the groups. A 32.5% treatment difference favoring liatermin in mean <jats:sup>18<\/jats:sup>F\u2010dopa influx constant (<jats:italic>p<\/jats:italic> = 0.019) was observed. Serious, device\u2010related adverse events required surgical repositioning of catheters in two patients and removal of devices in another. Neutralizing antiliatermin antibodies were detected in three patients (one on\u2010study and two in the open\u2010label extension).<\/jats:p><\/jats:sec><jats:sec><jats:title><jats:styled-content><jats:italic>Interpretation<\/jats:italic><\/jats:styled-content><\/jats:title><jats:p>Liatermin did not confer the predetermined level of clinical benefit to patients with PD despite increased <jats:sup>18<\/jats:sup>F\u2010dopa uptake. It is uncertain whether technical differences between this trial and positive open\u2010label studies contributed in any way this negative outcome. Ann Neurol 2006<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.20737","type":"journal-article","created":{"date-parts":[[2006,1,20]],"date-time":"2006-01-20T19:48:24Z","timestamp":1137786504000},"page":"459-466","source":"Crossref","is-referenced-by-count":811,"title":["Randomized controlled trial of intraputamenal glial cell line\u2013derived neurotrophic factor infusion in Parkinson disease"],"prefix":"10.1002","volume":"59","author":[{"given":"Anthony E.","family":"Lang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Gill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nik K.","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"Lozano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.","family":"Nutt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Penn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Brooks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Hotton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Moro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Heywood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Brodsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Burchiel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arif","family":"Dalvi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burton","family":"Scott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Stacy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Turner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. 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