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Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial.

Publication ,  Journal Article
Marks, WJ; Bartus, RT; Siffert, J; Davis, CS; Lozano, A; Boulis, N; Vitek, J; Stacy, M; Turner, D; Verhagen, L; Bakay, R; Watts, R; Stern, M ...
Published in: Lancet Neurol
December 2010

BACKGROUND: In an open-label phase 1 trial, gene delivery of the trophic factor neurturin via an adeno-associated type-2 vector (AAV2) was well tolerated and seemed to improve motor function in patients with advanced Parkinson's disease. We aimed to assess the safety and efficacy of AAV2-neurturin in a double-blind, phase 2 randomised trial. METHODS: We did a multicentre, double-blind, sham-surgery controlled trial in patients with advanced Parkinson's disease. Patients were randomly assigned (2:1) by a central, computer generated, randomisation code to receive either AAV2-neurturin (5·4 × 10¹¹ vector genomes) injected bilaterally into the putamen or sham surgery. All patients and study personnel with the exception of the neurosurgical team were masked to treatment assignment. The primary endpoint was change from baseline to 12 months in the motor subscore of the unified Parkinson's disease rating scale in the practically-defined off state. All randomly assigned patients who had at least one assessment after baseline were included in the primary analyses. This trial is registered at ClinicalTrials.gov, NCT00400634. RESULTS: Between December, 2006, and November, 2008, 58 patients from nine sites in the USA participated in the trial. There was no significant difference in the primary endpoint in patients treated with AAV2-neurturin compared with control individuals (difference -0·31 [SE 2·63], 95% CI -5·58 to 4·97; p=0·91). Serious adverse events occurred in 13 of 38 patients treated with AAV2-neurturin and four of 20 control individuals. Three patients in the AAV2-neurturin group and two in the sham surgery group developed tumours. INTERPRETATION: Intraputaminal AAV2-neurturin is not superior to sham surgery when assessed using the UPDRS motor score at 12 months. However, the possibility of a benefit with additional targeting of the substantia nigra and longer term follow-up should be investigated in further studies. FUNDING: Ceregene and Michael J Fox Foundation for Parkinson's Research.

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Published In

Lancet Neurol

DOI

EISSN

1474-4465

Publication Date

December 2010

Volume

9

Issue

12

Start / End Page

1164 / 1172

Location

England

Related Subject Headings

  • Treatment Outcome
  • Time Factors
  • Severity of Illness Index
  • Putamen
  • Parkinson Disease
  • Neurturin
  • Neurology & Neurosurgery
  • Motor Activity
  • Middle Aged
  • Male
 

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Marks, W. J., Bartus, R. T., Siffert, J., Davis, C. S., Lozano, A., Boulis, N., … Olanow, C. W. (2010). Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial. Lancet Neurol, 9(12), 1164–1172. https://doi.org/10.1016/S1474-4422(10)70254-4
Marks, William J., Raymond T. Bartus, Joao Siffert, Charles S. Davis, Andres Lozano, Nicholas Boulis, Jerrold Vitek, et al. “Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial.Lancet Neurol 9, no. 12 (December 2010): 1164–72. https://doi.org/10.1016/S1474-4422(10)70254-4.
Marks WJ, Bartus RT, Siffert J, Davis CS, Lozano A, Boulis N, et al. Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial. Lancet Neurol. 2010 Dec;9(12):1164–72.
Marks, William J., et al. “Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial.Lancet Neurol, vol. 9, no. 12, Dec. 2010, pp. 1164–72. Pubmed, doi:10.1016/S1474-4422(10)70254-4.
Marks WJ, Bartus RT, Siffert J, Davis CS, Lozano A, Boulis N, Vitek J, Stacy M, Turner D, Verhagen L, Bakay R, Watts R, Guthrie B, Jankovic J, Simpson R, Tagliati M, Alterman R, Stern M, Baltuch G, Starr PA, Larson PS, Ostrem JL, Nutt J, Kieburtz K, Kordower JH, Olanow CW. Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial. Lancet Neurol. 2010 Dec;9(12):1164–1172.
Journal cover image

Published In

Lancet Neurol

DOI

EISSN

1474-4465

Publication Date

December 2010

Volume

9

Issue

12

Start / End Page

1164 / 1172

Location

England

Related Subject Headings

  • Treatment Outcome
  • Time Factors
  • Severity of Illness Index
  • Putamen
  • Parkinson Disease
  • Neurturin
  • Neurology & Neurosurgery
  • Motor Activity
  • Middle Aged
  • Male