Dose response to intraventricular glial cell line-derived neurotrophic factor administration in parkinsonian monkeys.
A double-blinded study was conducted to evaluate the dose response of hemiparkinsonian rhesus monkeys to intracerebroventricular (ICV) injections of recombinant methionine human glial cell line-derived neurotrophic factor (GDNF). Thirty rhesus monkeys with stable hemiparkinsonian features were divided into six treatment groups (vehicle, 10, 30, 100, 300 and 1000 microg GDNF; n = 5/group). Each animal received 4 ICV administrations spaced at four week intervals. In addition, the animals were followed for 4 mo after the last injection. Standardized video taped behavioral tests were used to rate parkinsonian features using a nonhuman primate rating scale and assess side effects from treatment. Significant behavioral improvements were measured in animals receiving 100 to 1000 microg GDNF. One month after the last GDNF administration, parkinsonian features in animals receiving 100 and 1000 microg GDNF began to return to baseline levels. However, 300 microg GDNF recipients continued to display behavioral improvements. Parkinsonian features significantly improved were: bradykinesia, rigidity, posture and balance. The most common side effect was a transient weight loss after GDNF administration. Only one other side effect was observed, one animal receiving 1000 microg GDNF displayed dyskinetic movements. The results provide additional information for evaluating the possible clinical application of GDNF for treating Parkinson's disease.
Zhang
Z
Z
Anatomy and Neurobiology, University of Kentucky Medical Center, Lexington 40536-0084, USA.
Miyoshi
Y
Y
Lapchak
P A
PA
Collins
F
F
Hilt
D
D
Lebel
C
C
Kryscio
R
R
Gash
D M
DM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007276:Injections, Intraventricular; D020267:MPTP Poisoning; D008253:Macaca mulatta; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy*
D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents