Document Detail

Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial.
MedLine Citation:
PMID:  20970382     Owner:  NLM     Status:  MEDLINE    
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, 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.
William J Marks; Raymond T Bartus; Joao Siffert; Charles S Davis; Andres Lozano; Nicholas Boulis; Jerrold Vitek; Mark Stacy; Dennis Turner; Leonard Verhagen; Roy Bakay; Raymond Watts; Barton Guthrie; Joseph Jankovic; Richard Simpson; Michele Tagliati; Ron Alterman; Matthew Stern; Gordon Baltuch; Philip A Starr; Paul S Larson; Jill L Ostrem; John Nutt; Karl Kieburtz; Jeffrey H Kordower; C Warren Olanow
Publication Detail:
Type:  Clinical Trial, Phase II; Journal Article; Multicenter Study; Randomized Controlled Trial     Date:  2010-10-20
Journal Detail:
Title:  The Lancet. Neurology     Volume:  9     ISSN:  1474-4465     ISO Abbreviation:  Lancet Neurol     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-22     Completed Date:  2010-12-17     Revised Date:  2014-08-15    
Medline Journal Info:
Nlm Unique ID:  101139309     Medline TA:  Lancet Neurol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1164-72     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
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MeSH Terms
Analysis of Variance
Dependovirus / genetics,  physiology*
Double-Blind Method
Follow-Up Studies
Genetic Therapy / methods*
Middle Aged
Motor Activity / physiology
Neurturin / genetics*,  metabolism,  therapeutic use*
Parkinson Disease / genetics,  physiopathology,  therapy*
Putamen / metabolism,  physiology
Severity of Illness Index
Time Factors
Treatment Outcome
Reg. No./Substance:
0/NRTN protein, human; 0/Neurturin
Comment In:
Lancet Neurol. 2010 Dec;9(12):1142-3   [PMID:  21087733 ]
Curr Neurol Neurosci Rep. 2011 Aug;11(4):345-8   [PMID:  21505812 ]

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