{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:51:09Z","timestamp":1791816669602,"version":"4.3.4"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,6,10]],"date-time":"2015-06-10T00:00:00Z","timestamp":1433894400000},"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":[[2015,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>A 12\u2010month double\u2010blind sham\u2010surgery\u2013controlled trial assessing adeno\u2010associated virus type 2 (AAV2)\u2010neurturin injected into the putamen bilaterally failed to meet its primary endpoint, but showed positive results for the primary endpoint in the subgroup of subjects followed for 18 months and for several secondary endpoints. Analysis of postmortem tissue suggested impaired axonal transport of neurturin from putamen to substantia nigra. In the present study, we tested the safety and efficacy of AAV2\u2010neurturin delivered to putamen and substantia nigra.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a 15\u2010 to 24\u2010month, multicenter, double\u2010blind trial in patients with advanced Parkinson disease (PD) who were randomly assigned to receive bilateral AAV2\u2010neurturin injected bilaterally into the substantia nigra (2.0 \u00d7 10<jats:sup>11<\/jats:sup> vector genomes) and putamen (1.0 \u00d7 10<jats:sup>12<\/jats:sup> vector genomes) or sham surgery. The primary endpoint was change from baseline to final visit performed at the time the last enrolled subject completed the 15\u2010month evaluation in the motor subscore of the Unified Parkinson's Disease Rating Scale in the practically defined off state.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fifty\u2010one patients were enrolled in the trial. There was no significant difference between groups in the primary endpoint (change from baseline: AAV2\u2010neurturin, \u22127.0\u2009\u00b1\u20099.92; sham, \u22125.2\u2009\u00b1\u200910.01; <jats:italic>p<\/jats:italic>\u2009=\u20090.515) or in most secondary endpoints. Two subjects had cerebral hemorrhages with transient symptoms. No clinically meaningful adverse events were attributed to AAV2\u2010neurturin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>AAV2\u2010neurturin delivery to the putamen and substantia nigra bilaterally in PD was not superior to sham surgery. The procedure was well tolerated, and there were no clinically significant adverse events related to AAV2\u2010neurturin. Ann Neurol 2015;78:248\u2013257<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.24436","type":"journal-article","created":{"date-parts":[[2015,6,11]],"date-time":"2015-06-11T01:39:45Z","timestamp":1433986785000},"page":"248-257","source":"Crossref","is-referenced-by-count":252,"title":["Gene delivery of neurturin to putamen and substantia nigra in <scp>P<\/scp>arkinson disease: A double\u2010blind, randomized, controlled trial"],"prefix":"10.1002","volume":"78","author":[{"given":"C.","family":"Warren Olanow","sequence":"first","affiliation":[{"name":"Departments of Neurology and Neuroscience Mount Sinai School of Medicine New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond T.","family":"Bartus","sequence":"additional","affiliation":[{"name":"RTBioconsultants San Diego CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany L.","family":"Baumann","sequence":"additional","affiliation":[{"name":"Isis Pharmaceuticals  Carlsbad CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stewart","family":"Factor","sequence":"additional","affiliation":[{"name":"Department of Neurology Emory University School of Medicine Atlanta GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Boulis","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Emory University School of Medicine Atlanta GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Stacy","sequence":"additional","affiliation":[{"name":"Department of Neurology Duke University School of Medicine Durham NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis A.","family":"Turner","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Duke University School of Medicine Durham NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Marks","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery University of California, San Francisco San Francisco CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Larson","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery University of California, San Francisco San Francisco CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip A.","family":"Starr","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery University of California, San Francisco San Francisco CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Jankovic","sequence":"additional","affiliation":[{"name":"Department of Neurology Baylor College of Medicine Houston TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Simpson","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Baylor College of Medicine Houston TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ray","family":"Watts","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Alabama at Birmingham Birmingham AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barton","family":"Guthrie","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery University of Alabama at Birmingham Birmingham AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Poston","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences Stanford University Medical Center Stanford CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaimie M.","family":"Henderson","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Stanford University Medical Center Stanford CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Stern","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pennsylvania Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon","family":"Baltuch","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery University of Pennsylvania Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher G.","family":"Goetz","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences Rush University Medical Center Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Herzog","sequence":"additional","affiliation":[{"name":"Ceregene San Diego CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey H.","family":"Kordower","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences Rush University Medical Center Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron","family":"Alterman","sequence":"additional","affiliation":[{"name":"Beth Israel\u2013Deaconess Medical Center, Department of Neurosurgery Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres M.","family":"Lozano","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, Department of Surgery Toronto Western Hospital, University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony E.","family":"Lang","sequence":"additional","affiliation":[{"name":"Division of Neurology Department of Medicine University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,6,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/380252a0"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5492.767"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.60.1.69"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20737"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199909)46:3<419::AID-ANA21>3.0.CO;2-Q"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2006.07.015"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/384467a0"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21503"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21032"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300010"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2008.170"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70065-6"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70254-4"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23442"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2015.03.023"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.45"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2009.103"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2013.04.011"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.05.026"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182904faa"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2013.281"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004676"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5427-08.2009"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt192"},{"key":"e_1_2_8_26_1","unstructured":"BartusRT.CERE\u2010120 (AAV2\u2010NRTN) for the treatment of Parkinson's disease: experience from 4 clinical trials and human autopsy data. Paper presented at: Sixteen Annual Meeting of the American Society for Gene and Cell Therapy (ASGCT); May 17 2013; Salt Lake City UT."},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22453"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.24436","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.24436","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,7]],"date-time":"2023-10-07T00:07:57Z","timestamp":1696637277000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.24436"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,10]]},"references-count":26,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2015,8]]}},"alternative-id":["10.1002\/ana.24436"],"URL":"https:\/\/doi.org\/10.1002\/ana.24436","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,10]]}}}