Basal ganglia lesions after MPTP administration in rhesus monkeys.
In monkeys, intracarotid infusion of a single low dose of MPTP reliably induces a hemiparkinsonian syndrome that is stable over time. This model has been widely used to assess novel anti-parkinsonian therapies. Here, we report the exceptional finding of severe necrotic lesions that were observed in the basal ganglia (but not in the substantia nigra) of monkeys that received a single intracarotid injection of MPTP followed by gene therapy treatments. Although extensive unilateral dopaminergic nigrostriatal loss was found in all the animals, partial behavioral recovery was observed in the subjects that presented pallidal necrotic lesions. This report discusses possible causes and effects of the necrotic lesions and their locations and the value of the intracarotid MPTP model. Testing novel therapies in monkey models has become an essential step before clinical trials. These results indicate that evaluation of any treatment should consider possible confounding factors that may affect the results.
Emborg
M E
ME
Wisconsin National Primate Research Center, University of Wisconsin-Madison, 53715, USA. emborg@primate.wisc.edu
Moirano
J
J
Schafernak
K T
KT
Moirano
M
M
Evans
M
M
Konecny
T
T
Roitberg
B
B
Ambarish
P
P
Mangubat
E
E
Ma
Y
Y
Eidelberg
D
D
Holden
J
J
Kordower
J H
JH
Leestma
J E
JE
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000473:pathology*; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics* / Q000627:therapeutic use; D008253:Macaca mulatta; D008297:Male; D009498:Neurotoxins; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology / Q000628:therapy
D051100:Glial Cell Line-Derived Neurotrophic Factor; D009498:Neurotoxins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine