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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • Anthony E. Lang, University of Toronto
  • ,
  • Steven Gill, Frenchay Hospital
  • ,
  • Nik K. Patel, Frenchay Hospital
  • ,
  • Andres Lozano, Toronto Western Research Institute University of Toronto
  • ,
  • John G. Nutt, Oregon Health and Science University
  • ,
  • Richard Penn, University of Chicago, Chicago, Illinois.
  • ,
  • David J. Brooks
  • Gary Hotton, Hammersmith Hospital
  • ,
  • Elena Moro, University of Toronto
  • ,
  • Peter Heywood, University of Toronto
  • ,
  • Matthew A. Brodsky, Oregon Health and Science University
  • ,
  • Kim Burchiel, Oregon Health and Science University
  • ,
  • Patrick Kelly, New York University Medical Center
  • ,
  • Arif Dalvi, University of Chicago, Chicago, Illinois.
  • ,
  • Burton Scott, Duke Movement Disorders Clinic
  • ,
  • Mark Stacy, Duke University
  • ,
  • Dennis Turner, Duke University
  • ,
  • V. G.Frederich Wooten, Virginia Commonwealth University, Virginia
  • ,
  • William J. Elias, Virginia Commonwealth University, Virginia
  • ,
  • Edward R. Laws, Virginia Commonwealth University, Virginia
  • ,
  • Vijay Dhawan, North Shore Long Island Jewish Research Institute
  • ,
  • A. Jon Stoessl, The University of British Columbia
  • ,
  • James Matcham, Amgen Ltd.
  • ,
  • Robert J. Coffey, Medtronic Inc.
  • ,
  • Michael Traub, Amgen Inc.

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.

Original languageEnglish
JournalAnnals of Neurology
Volume59
Issue3
Pages (from-to)459-466
Number of pages8
ISSN0364-5134
DOIs
Publication statusPublished - 1 Mar 2006
Externally publishedYes

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