Modeling Parkinson's disease in monkeys for translational studies, a critical analysis.
The non-human primate MPTP model of Parkinson's disease is an essential tool for translational studies. However, the currently used methodologies to produce parkinsonian monkeys do not follow unified criteria, and the applied models may often fall short of reproducing the characteristics of patients in clinical trials. Pooling of data from the parkinsonian monkeys produced in our Centers provided the opportunity to evaluate thoroughly the behavioral outcomes that may be considered for appropriate modeling in preclinical studies. We reviewed records from 108 macaques including rhesus and cynomolgus species used to model moderate to advanced parkinsonism with systemic MPTP treatment. The attained motor disability and the development of levodopa-induced dyskinesias, as primary outcomes, and the occurrence of clinical complications and instability of symptoms were all analyzed for correlations with the parameters of MPTP administration and for estimation of sample sizes. Results showed that frequently the MPTP-treated macaque can recapitulate the phenotype of patients entering clinical trials, but to produce this model consistently it is important to adapt the MPTP exposure tightly according to individual animal responses. For studies of reduced animal numbers it is also important to produce stable models, and stability of parkinsonism in macaques critically depends on reaching "marked" motor disability. The analyzed data also led to put forward recommendations for successfully producing the primate MPTP model of Parkinson's disease for translational studies.
Yerkes National Primate Research Center, Emory University School of Medicine, Neuroscience Building, Atlanta, GA 30329, USA.
Lisa F
LF
Potts
Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
Hao
H
Wu
Yerkes National Primate Research Center, Emory University School of Medicine, Neuroscience Building, Atlanta, GA 30329, USA.
Arun
A
Singh
Laboratory of Regenerative Therapy, Department of Neurology and Neuroscience Division, Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
Irene
I
Marcilla
Laboratory of Regenerative Therapy, Department of Neurology and Neuroscience Division, Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
Maria R
MR
Luquin
Yerkes National Primate Research Center, Emory University School of Medicine, Neuroscience Building, Atlanta, GA 30329, USA; Department of Neurology, Emory University School of Medicine, 6000 WMRC, 101 Woodruff Circle, Atlanta, GA 30322, USA. Electronic address: spapa@emory.edu.
Stella M
SM
Papa
D000818:Animals; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D020267:MPTP Poisoning / Q000188:drug therapy*; D008251:Macaca; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy*
Dyskinesia; MPTP; Model; Non-human primate; Parkinson's disease