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.