• Warren OlanowCCDepartments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, NY., Raymond T Bartus, Tiffany L Baumann, Stewart Factor, Nicholas Boulis, Mark Stacy, Dennis A Turner, William Marks, Paul Larson, Phillip A Starr, Joseph Jankovic, Richard Simpson, Ray Watts, Barton Guthrie, Kathleen Poston, Jaimie M Henderson, Matthew Stern, Gordon Baltuch, Christopher G Goetz, Christopher Herzog, Jeffrey H Kordower, Ron Alterman, Andres M Lozano, and Anthony E Lang.
• Departments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, NY.
• Ann. Neurol. 2015 Aug 1; 78 (2): 248-57.

ObjectiveA 12-month double-blind sham-surgery-controlled trial assessing adeno-associated virus type 2 (AAV2)-neurturin 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-neurturin delivered to putamen and substantia nigra.MethodsWe performed a 15- to 24-month, multicenter, double-blind trial in patients with advanced Parkinson disease (PD) who were randomly assigned to receive bilateral AAV2-neurturin injected bilaterally into the substantia nigra (2.0 × 10(11) vector genomes) and putamen (1.0 × 10(12) 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-month evaluation in the motor subscore of the Unified Parkinson's Disease Rating Scale in the practically defined off state.ResultsFifty-one patients were enrolled in the trial. There was no significant difference between groups in the primary endpoint (change from baseline: AAV2-neurturin, -7.0 ± 9.92; sham, -5.2 ± 10.01; p = 0.515) or in most secondary endpoints. Two subjects had cerebral hemorrhages with transient symptoms. No clinically meaningful adverse events were attributed to AAV2-neurturin.InterpretationAAV2-neurturin 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-neurturin.© 2015 American Neurological Association.

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