Gene therapy for late infantile neuronal ceroid lipofuscinosis: Neurosurgical considerations

Mark M. Souweidane, Justin F. Fraser, Lisa M. Arkin, Dolan Sondhi, Neil R. Hackett, Stephen M. Kaminsky, Linda Heier, Barry E. Kosofsky, Stefan Worgall, Ronald G. Crystal, Michael G. Kaplitt

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


Object. The authors conducted a phase I study of late infantile neuronal ceroid lipofuscinosis using an adeno-associated virus serotype 2 (AAV2) vector containing the deficient CLN2 gene (AAV2CUhCLN2). The operative technique, radiographic changes, and surgical complications are presented. Methods. Ten patients with late infantile neuronal ceroid lipofuscinosis disease each underwent infusion of AAV2CUhCLN2 (3 × 1012 particle units) into 12 distinct cerebral locations (2 depths/bur hole, 75 minutes/infusion, and 2 μl/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. Results. Radiographically demonstrated changes were seen in 39 (65%) of 60 injection sites, confirming localization and infusion. There were no radiographically or clinically defined complications. Conclusions. The 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.

Original languageEnglish
Pages (from-to)115-122
Number of pages8
JournalJournal of Neurosurgery: Pediatrics
Issue number2
StatePublished - Aug 2010


  • Gene therapy
  • Lipofuscinosis
  • Local delivery
  • Storage disease

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology


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