Journal
ANNALS OF NEUROLOGY
Volume 59, Issue 3, Pages 459-466Publisher
WILEY-LISS
DOI: 10.1002/ana.20737
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Funding
- Medical Research Council [MC_U120036861] Funding Source: researchfish
- Medical Research Council [MC_U120036861] Funding Source: Medline
- MRC [MC_U120036861] Funding Source: UKRI
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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). Metho Thirty-four PD patients were randomized 1 to 1 to receive bilateral continuous Ipu infusion of liatermin 15 mu g/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 F-18-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 F-18-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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