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

AbstractOBJECT:
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.
AuthorsJohn T Slevin, Greg A Gerhardt, Charles D Smith, Don M Gash, Richard Kryscio, Byron Young
JournalJournal of neurosurgery (J Neurosurg) Vol. 102 Issue 2 Pg. 216-22 (Feb 2005) ISSN: 0022-3085 [Print] United States
PMID15739547 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antiparkinson Agents
  • GDNF protein, human
  • Glial Cell Line-Derived Neurotrophic Factor
  • Nerve Growth Factors
Topics
  • Aged
  • Antiparkinson Agents (administration & dosage)
  • Dominance, Cerebral (drug effects, physiology)
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Gait (drug effects, physiology)
  • Glial Cell Line-Derived Neurotrophic Factor
  • Humans
  • Infusion Pumps, Implantable
  • Male
  • Middle Aged
  • Motor Activity (drug effects, physiology)
  • Nerve Growth Factors (administration & dosage)
  • Parkinson Disease (diagnosis, drug therapy, physiopathology)
  • Postural Balance (drug effects, physiology)
  • Psychomotor Performance (drug effects, physiology)
  • Putamen (drug effects, physiopathology)
  • Reaction Time (drug effects, physiology)
  • Treatment Outcome

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