Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease

Objective Glial cell line–derived neurotrophic factor (GDNF) exerts potent trophic influence on midbrain dopaminergic neurons. This randomized controlled clinical trial was designed to confirm initial clinical benefits observed in a small, open‐label trial using intraputamenal (Ipu) infusion of reco...

Full description

Saved in:
Bibliographic Details
Published in:Annals of neurology 2006-03, Vol.59 (3), p.459-466
Main Authors: Lang, Anthony E., Gill, Steven, Patel, Nik K., Lozano, Andres, Nutt, John G., Penn, Richard, Brooks, David J., Hotton, Gary, Moro, Elena, Heywood, Peter, Brodsky, Matthew A., Burchiel, Kim, Kelly, Patrick, Dalvi, Arif, Scott, Burton, Stacy, Mark, Turner, Dennis, Wooten, V. G. Frederich, Elias, William J., Laws, Edward R., Dhawan, Vijay, Stoessl, A. Jon, Matcham, James, Coffey, Robert J., Traub, Michael
Format: Article
Language:English
Subjects:
Adult
Analysis of Variance
Biological and medical sciences
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Dihydroxyphenylalanine - metabolism
Dose-Response Relationship, Drug
Double-Blind Method
Drug Delivery Systems
Drug Evaluation
Female
Glial Cell Line-Derived Neurotrophic Factor - therapeutic use
Humans
Male
Medical sciences
Middle Aged
Neurology
Neuropharmacology
Neuroprotective agent
Parkinson Disease - diagnostic imaging
Parkinson Disease - drug therapy
Parkinson Disease - metabolism
Pharmacology. Drug treatments
Positron-Emission Tomography - methods
Putamen - diagnostic imaging
Putamen - drug effects
Putamen - metabolism
Recombinant Proteins - therapeutic use
Severity of Illness Index
Time Factors
Treatment Outcome
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Objective Glial cell line–derived neurotrophic factor (GDNF) exerts potent trophic influence on midbrain dopaminergic neurons. This randomized controlled clinical trial was designed to confirm initial clinical benefits observed in a small, open‐label trial using intraputamenal (Ipu) infusion of recombinant human GDNF (liatermin). Methods Thirty‐four PD patients were randomized 1 to 1 to receive bilateral continuous Ipu infusion of liatermin 15μg/putamen/day or placebo. The primary end point was the change in Unified Parkinson Disease Rating Scale (UPDRS) motor score in the practically defined off condition at 6 months. Secondary end points included other UPDRS scores, motor tests, dyskinesia ratings, patient diaries, and 18F‐dopa uptake. Results At 6 months, mean percentage changes in “off” UPDRS motor score were −10.0% and −4.5% in the liatermin and placebo groups, respectively. This treatment difference was not significant (95% confidence interval, −23.0 to 12.0, p = 0.53). Secondary end point results were similar between the groups. A 32.5% treatment difference favoring liatermin in mean 18F‐dopa influx constant (p = 0.019) was observed. Serious, device‐related adverse events required surgical repositioning of catheters in two patients and removal of devices in another. Neutralizing antiliatermin antibodies were detected in three patients (one on‐study and two in the open‐label extension). Interpretation Liatermin did not confer the predetermined level of clinical benefit to patients with PD despite increased 18F‐dopa uptake. It is uncertain whether technical differences between this trial and positive open‐label studies contributed in any way this negative outcome. Ann Neurol 2006
ISSN:0364-5134
1531-8249
DOI:10.1002/ana.20737