Dose response to intraventricular glial cell line-derived neurotrophic factor administration in Parkinsonian monkeys

Zhiming Zhang, Yasuyuki Miyoshi, Paul A. Lapchak, Frank Collins, Dana Hilt, Carl Lebel, Richard Kryscio, Don M. Gash

Research output: Contribution to journalArticlepeer-review

117 Scopus citations

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 improve merits 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.

Original languageEnglish
Pages (from-to)1396-1401
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume282
Issue number3
StatePublished - Sep 1997

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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