Abstract
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 μg 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 μg GDNF. One month after the last GDNF administration, parkinsonian features in animals receiving 100 and 1000 μg GDNF began to return to baseline levels. However, 300 μg 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 μg GDNF displayed dyskinetic movements. The results provide additional information for evaluating the possible clinical application of GDNF for treating Parkinson’s disease.
Footnotes
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Send reprint requests to: Dr. Don Marshall Gash, Anatomy and Neurobiology, University of Kentucky Medical Center, 800 Rose Street, MN224, Lexington, KY 40536-0084.
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↵1 This study was supported by a contract with Amgen, Inc., Thousand Oaks, CA.
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↵2 Current address: Department of Anatomy and Neurobiology, University of Kentucky, College of Medicine, Lexington, KY 40536.
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↵3 Current address: Department of Biostatistics, University of Kentucky, Lexington, KY 40536.
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↵4 Current address: Department of Neuroscience, Amgen, Inc., Thousand Oaks, CA 91320.
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↵5 Current address: Department of Clinical Development, Amgen, Inc., Thousand Oaks, CA 91320
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↵6 Current address: Department of Toxicology, Amgen, Inc., Thousand Oaks, CA 91320.
- Abbreviations:
- GDNF
- glial cell line-derived neurotrophic factor
- MPTP
- 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
- ICV
- intracerebroventricular
- Received January 17, 1997.
- Accepted May 2, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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