Gene delivery of neurturin to putamen and substantia nigra in Parkinson disease: A double-blind, randomized, controlled trial.

Published

Journal Article

OBJECTIVE: A 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. METHODS: We 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. RESULTS: Fifty-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. INTERPRETATION: AAV2-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.

Full Text

Duke Authors

Cited Authors

  • Warren Olanow, C; Bartus, RT; Baumann, TL; Factor, S; Boulis, N; Stacy, M; Turner, DA; Marks, W; Larson, P; Starr, PA; Jankovic, J; Simpson, R; Watts, R; Guthrie, B; Poston, K; Henderson, JM; Stern, M; Baltuch, G; Goetz, CG; Herzog, C; Kordower, JH; Alterman, R; Lozano, AM; Lang, AE

Published Date

  • August 2015

Published In

Volume / Issue

  • 78 / 2

Start / End Page

  • 248 - 257

PubMed ID

  • 26061140

Pubmed Central ID

  • 26061140

Electronic International Standard Serial Number (EISSN)

  • 1531-8249

International Standard Serial Number (ISSN)

  • 0364-5134

Digital Object Identifier (DOI)

  • 10.1002/ana.24436

Language

  • eng