Extended Treatment with Glial Cell Line-Derived Neurotrophic Factor in Parkinson's Disease

Alan L Whone, Mihaela Boca, Matthias Luz, Max Woolley, Lucy Mooney, Sonali Dharia, Jack Broadfoot, David Cronin, Christian Schroers, Neil U Barua, Lara Longpre, C Lynn Barclay, Chris Boiko, Greg A Johnson, H Christian Fibiger, Rob Harrison, Owen Lewis, Gemma Pritchard, Mike Howell, Charlie IrvingDavid Johnson, Suk Kinch, Christopher Marshall, Andrew D Lawrence, Stephan Blinder, Vesna Sossi, A Jon Stoessl, Paul Skinner, Erich Mohr, Steven S Gill

Research output: Contribution to journalArticle (Academic Journal)peer-review

71 Citations (Scopus)
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BACKGROUND: Intraputamenal glial cell line-derived neurotrophic factor (GDNF), administered every 4 weeks to patients with moderately advanced Parkinson's disease, did not show significant clinical improvements against placebo at 40 weeks, although it significantly increased [18F]DOPA uptake throughout the entire putamen.

OBJECTIVE: This open-label extension study explored the effects of continued (prior GDNF patients) or new (prior placebo patients) exposure to GDNF for another 40 weeks.

METHODS: Using the infusion protocol of the parent study, all patients received GDNF without disclosing prior treatment allocations (GDNF or placebo). The primary outcome was the percentage change from baseline to Week 80 in the OFF state Unified Parkinson's Disease Rating Scale (UPDRS) motor score.

RESULTS: All 41 parent study participants were enrolled. The primary outcome decreased by 26.7±20.7% in patients on GDNF for 80 weeks (GDNF/GDNF; N = 21) and 27.6±23.6% in patients on placebo for 40 weeks followed by GDNF for 40 weeks (placebo/GDNF, N = 20; least squares mean difference: 0.4%, 95% CI: -13.9, 14.6, p = 0.96). Secondary endpoints did not show significant differences between the groups at Week 80 either. Prespecified comparisons between GDNF/GDNF at Week 80 and placebo/GDNF at Week 40 showed significant differences for mean OFF state UPDRS motor (-9.6±6.7 vs. -3.8±4.2 points, p = 0.0108) and activities of daily living score (-6.9±5.5 vs. -1.0±3.7 points, p = 0.0003). No treatment-emergent safety concerns were identified.

CONCLUSIONS: The aggregate study results, from the parent and open-label extension suggest that future testing with GDNF will likely require an 80- rather than a 40-week randomized treatment period and/or a higher dose.

Original languageEnglish
Pages (from-to)301-313
Number of pages13
JournalJournal of Parkinson's Disease
Issue number2
Publication statusPublished - 23 May 2019


  • glial cell line-derived neurotrophic factor
  • convection enhanced delivery
  • Parkinson's disease
  • neurorestoration


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