title: Comparison of fetal mesencephalic grafts, AAV-delivered GDNF, and both combined in an MPTP-induced nonhuman primate Parkinson's model.
abstract: We combined viral vector delivery of human glial-derived neurotrophic factor (GDNF) with the grafting of dopamine (DA) precursor cells from fetal ventral mesencephalon (VM) to determine whether these strategies would improve the anti-Parkinson's effects in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, an animal model for Parkinson's disease (PD). Both strategies have been reported as individually beneficial in animal models of PD, leading to clinical studies. GDNF delivery has also been reported to augment VM tissue implants, but no combined studies have been done in monkeys. Monkeys were treated with MPTP and placed into four balanced treatment groups receiving only recombinant adeno-associated virus serotype 5 (rAAV5)/hu-GDNF, only fetal DA precursor cells, both together, or a buffered saline solution (control). The combination of fetal precursors with rAAV5/hu-GDNF showed significantly higher striatal DA concentrations compared with the other treatments, but did not lead to greater functional improvement in this study. For the first time under identical conditions in primates, we show that all three treatments lead to improvement compared with control animals.
authors.affiliation: 1] Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA [2] Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: D Eugene
authors.initials: DE
authors.lastname: Redmond
authors.forename: Caleb R S
authors.initials: CR
authors.lastname: McEntire
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Kingsbery
authors.forename: Csaba
authors.initials: C
authors.lastname: Leranth
authors.forename: John D
authors.initials: JD
authors.lastname: Elsworth
authors.forename: Kimberly B
authors.initials: KB
authors.lastname: Bjugstad
authors.forename: Robert H
authors.initials: RH
authors.lastname: Roth
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Samulski
authors.forename: John R
authors.initials: JR
authors.lastname: Sladek
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D016380:Brain Tissue Transplantation; D002522:Chlorocebus aethiops; D003131:Combined Modality Therapy; D003342:Corpus Striatum / Q000378:metabolism / Q000503:physiopathology; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000166:cytology / Q000378:metabolism; D016332:Fetal Tissue Transplantation; D015316:Genetic Therapy; D005822:Genetic Vectors; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D004860:Infectious Anemia Virus, Equine / Q000235:genetics; D020267:MPTP Poisoning / Q000503:physiopathology / Q000523:psychology / Q000628:therapy*; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000637:transplantation*; D010300:Parkinson Disease / Q000503:physiopathology / Q000523:psychology / Q000628:therapy*
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D004298:Dopamine
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