Improvement of bilateral motor functions in patients with Parkinson disease through the unilateral intraputaminal infusion of glial cell line—derived neurotrophic factor

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Object. Glial cell line-derived neurotrophic factor (GDNF) has demonstrated significant antiparkinsonian actions in several animal models and in a recent pilot study in England in which four of five patients received bilateral putaminal delivery. In the present study the authors report on a 6-month unilateral intraputaminal GDNF infusion in 10 patients with advanced Parkinson disease (PD).

Methods. Patients with PD in a functionally defined on and off state were evaluated 1 week before and 1 and 4 weeks after intraputaminal catheter implantation in the side contralateral to the most affected side. Each patient was placed on a dose-escalation regimen of GDNF: 3, 10, and 30 µg/day at successive 8-week intervals, followed by a 1-month wash-out period.

The Unified Parkinson's Disease Rating Scale (UPDRS) total scores in the on and off states significantly improved 34 and 33%, respectively, at 24 weeks compared with baseline scores (95% confidence interval [CI] 18–47% for off scores and 16–51% for on scores). In addition, UPDRS motor scores in both the on and off states significantly improved by 30% at 24 weeks compared with baseline scores (95% CI 15–48% for off scores and 5–61% for on scores). Improvements occurred bilaterally, as measured by balance and gait and increased speed of hand movements. All significant improvements of motor function continued through the wash-out period. The only observed side effects were transient Lhermitte symptoms in two patients.

Conclusions. Analysis of the data in this open-label study demonstrates the safety and potential efficacy of unilateral intraputaminal GDNF infusion. Unilateral administration of the protein resulted in significant, sustained bilateral effects.

Article Information

Address reprint requests to: John T. Slevin, M.D., Department of Neurology, University of Kentucky Medical Center, Kentucky Clinic (Wing D)-L445, Lexington, Kentucky 40536–0284. email: jslevin@uky.edu.

© AANS, except where prohibited by US copyright law.

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Figures

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    Left: Illustration depicting catheter locations represented by white circles (except in the patient in Case 6, who is represented by a black circle for clarity). Images were normalized to the Talairach atlas, and the catheter locations were mapped to a single axial slice level (± 4 mm). The target for catheter placement was the mid-dorsal putamen. Numbers represent the corresponding case number. The reference anatomical underlay is the Talairach-nor-malized average T1-weighted MR image with a superimposed lenticular nucleus map (dark gray indicates the putamen; light gray indicates the globus pallidus) from the 10 patients. L = patient left. Bar = 10 mm. Right: Schematic of infusion system. L = lateral ventricle; P = putamen.

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    Graphs demonstrating the UPDRS total and motor scores for each patient in the on and off states. Individual results from patients in Cases 1 through 10 (P1–P10) are shown for the study period.

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