Abstract | 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 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.
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Authors | John T Slevin, Greg A Gerhardt, Charles D Smith, Don M Gash, Richard Kryscio, Byron Young |
Journal | Journal of neurosurgery
(J Neurosurg)
Vol. 102
Issue 2
Pg. 216-22
(Feb 2005)
ISSN: 0022-3085 [Print] United States |
PMID | 15739547
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antiparkinson Agents
- GDNF protein, human
- Glial Cell Line-Derived Neurotrophic Factor
- Nerve Growth Factors
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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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