Improvement of bilateral motor functions in patients with Parkinson disease through the unilateral intraputaminal infusion of glial cell line-derived neurotrophic factor.
OBJECTIVE
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 microg/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.
Slevin
John T
JT
Department of Anatomy and Neurobiology, Morris K. Udall Parkinson's Disease Research Center of Excellence, University of Kentucky, Lexington 40536-0284, USA. jslevin@uky.edu
Gerhardt
Greg A
GA
Smith
Charles D
CD
Gash
Don M
DM
Kryscio
Richard
R
Young
Byron
B
D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage*; D004292:Dominance, Cerebral / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005684:Gait / Q000187:drug effects / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D015918:Infusion Pumps, Implantable; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009414:Nerve Growth Factors / Q000008:administration & dosage*; D010300:Parkinson Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D004856:Postural Balance / Q000187:drug effects / Q000502:physiology; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D011699:Putamen / Q000187:drug effects* / Q000503:physiopathology; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
D000978:Antiparkinson Agents; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors