Abstract:
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.
journal_name
Ann Neuroljournal_title
Annals of neurologyauthors
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,Altdoi
10.1002/ana.24436subject
Has Abstractpub_date
2015-08-01 00:00:00pages
248-57issue
2eissn
0364-5134issn
1531-8249journal_volume
78pub_type
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