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 recombinant human GDNF (liatermin). METHODS Thirty-four PD patients were randomized 1 to 1 to receive bilateral continuous Ipu infusion of liatermin 15 microg/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 (18)F-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 (18)F-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 (18)F-dopa uptake. It is uncertain whether technical differences between this trial and positive open-label studies contributed in any way this negative outcome.

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@article{Lang2006RandomizedCT, title={Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease.}, author={Anthony E Lang and Steven S Gill and Nik K Patel and Andres M. Lozano and John Nutt and Richard D. Penn and David J. Brooks and Gary R Hotton and Elena Moro and Peter Heywood and Matthew A. Brodsky and Kim Burchiel and Patrick Kelly and Arif Dalvi and Burton L. Scott and Mark Stacy and Dennis A. Turner and Virgil Wooten and W. Jeffrey Elias and Edward R. Laws and Vijay Dhawan and A. Jon Stoessl and James Matcham and Robert J Coffey and Michael Traub}, journal={Annals of neurology}, year={2006}, volume={59 3}, pages={459-66} }