{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:02:04Z","timestamp":1790866924673,"version":"4.1.0"},"reference-count":29,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["PED"],"published-print":{"date-parts":[[2010,8]]},"abstract":"\nObject<\/jats:title>\nThe authors conducted a phase I study of late infantile neuronal ceroid lipofuscinosis using an adenoassociated virus serotype 2 (AAV2) vector containing the deficient CLN2<\/jats:italic> gene (AAV2CU<\/jats:sub>hCLN2). The operative technique, radiographic changes, and surgical complications are presented.<\/jats:p><\/jats:sec>\n\nMethods<\/jats:title>\nTen patients with late infantile neuronal ceroid lipofuscinosis disease each underwent infusion of AAV2CU<\/jats:sub>hCLN2 (3 \u00d7 1012<\/jats:sup> particle units) into 12 distinct cerebral locations (2 depths\/bur hole, 75 minutes\/infusion, and 2 \u03bcl\/minute). Innovative surgical techniques were developed to overcome several obstacles for which little or no established techniques were available. Successful infusion relied on preoperative stereotactic planning to optimize a parenchymal target and diffuse administration. Six entry sites, each having 2 depths of injections, were used to reduce operative time and enhance distribution. A low-profile rigid fixation system with 6 integrated holding arms was utilized to perform simultaneous infusions within a practical time frame. Dural sealant with generous irrigation was used to avoid CSF egress with possible subdural hemorrhage or altered stereotactic registration.<\/jats:p><\/jats:sec>\n\nResults<\/jats:title>\nRadiographically demonstrated changes were seen in 39 (65%) of 60 injection sites, confirming localization and infusion. There were no radiographically or clinically defined complications.<\/jats:p><\/jats:sec>\n\nConclusions<\/jats:title>\nThe neurosurgical considerations and results of this study are presented to offer guidance and a basis for the design of future gene therapy or other clinical trials in children that utilize direct therapeutic delivery.<\/jats:p><\/jats:sec>","DOI":"10.3171\/2010.4.peds09507","type":"journal-article","created":{"date-parts":[[2010,7,30]],"date-time":"2010-07-30T13:36:31Z","timestamp":1280496991000},"page":"115-122","source":"Crossref","is-referenced-by-count":62,"title":["Gene therapy for late infantile neuronal ceroid lipofuscinosis: neurosurgical considerations"],"prefix":"10.3171","volume":"6","author":[{"given":"Mark M.","family":"Souweidane","sequence":"first","affiliation":[{"name":"Departments of Neurological Surgery,"},{"name":"Pediatrics, Weill Cornell Medical College, Cornell University, New York, New York; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin F.","family":"Fraser","sequence":"additional","affiliation":[{"name":"Departments of Neurological Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M.","family":"Arkin","sequence":"additional","affiliation":[{"name":"University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolan","family":"Sondhi","sequence":"additional","affiliation":[{"name":"Genetic Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil R.","family":"Hackett","sequence":"additional","affiliation":[{"name":"Genetic Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Kaminsky","sequence":"additional","affiliation":[{"name":"Genetic Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Heier","sequence":"additional","affiliation":[{"name":"Radiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry E.","family":"Kosofsky","sequence":"additional","affiliation":[{"name":"Pediatrics, Weill Cornell Medical College, Cornell University, New York, New York; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Worgall","sequence":"additional","affiliation":[{"name":"Genetic Medicine,"},{"name":"Pediatrics, Weill Cornell Medical College, Cornell University, New York, New York; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald G.","family":"Crystal","sequence":"additional","affiliation":[{"name":"Genetic Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Kaplitt","sequence":"additional","affiliation":[{"name":"Departments of Neurological Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1-0060115","series-title":"Hum Gene Ther","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1089\/hum.2005.16.1028","article-title":"Confronting the issues of therapeutic misconception, enrollment decisions, and personal motives in genetic medicine-based clinical research studies for fatal disorders","volume":"16","author":"Arkin","year":"2005"},{"key":"b2-0060115","series-title":"Neurology","doi-asserted-by":"publisher","first-page":"1662","DOI":"10.1212\/WNL.0b013e3181c29356","article-title":"Safety and tolerability of putaminal AADC gene therapy for Parkinson disease","volume":"73","author":"Christine","year":"2009"},{"key":"b3-0060115","series-title":"Hum Gene Ther","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1089\/hum.2004.15.1131","article-title":"Clinical protocol. 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