title: Encapsulated GDNF-producing C2C12 cells for Parkinson's disease: a pre-clinical study in chronic MPTP-treated baboons.
abstract: Glial cell line-derived neurotrophic factor (GDNF), a potent neurotrophic factor with restorative effects in a variety of rodent and primate models of Parkinson's disease (PD), could be of therapeutic value to PD. In this study, we show that intraventricular chronic infusion of low doses of GDNF using encapsulated genetically engineered C2C12 cells can exert: (1) transient recovery of motor deficits (hypokinesia); (2) significant protection of intrinsic striatal dopaminergic function in the immediate vicinity of the site of implantation of the capsule in the caudate nucleus, and (3) significant-long-lasting-neurotrophic properties at the nigral level with an increase volume of the cell bodies. These observations confirm the potent neurorestorative potential of GDNF in PD and the safety/efficacy of the encapsulation technology as a means to deliver in situ this neurotrophic cytokine even using an intraventricular approach.
authors.affiliation: Research Associate Unit URA CEA CNRS 2210, Service Hospitalier Frédéric Joliot, Orsay, France.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kishima
authors.forename: Thomas
authors.initials: T
authors.lastname: Poyot
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Bloch
authors.forename: Julien
authors.initials: J
authors.lastname: Dauguet
authors.forename: Françoise
authors.initials: F
authors.lastname: Condé
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dollé
authors.forename: Françoise
authors.initials: F
authors.lastname: Hinnen
authors.forename: William
authors.initials: W
authors.lastname: Pralong
authors.forename: Stéphane
authors.initials: S
authors.lastname: Palfi
authors.forename: Nicole
authors.initials: N
authors.lastname: Déglon
authors.forename: Patrick
authors.initials: P
authors.lastname: Aebischer
authors.forename: Philippe
authors.initials: P
authors.lastname: Hantraye
mesh_terms: D000818:Animals; D002214:Capsules; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives*; D005462:Fluorine Radioisotopes; D015316:Genetic Therapy / Q000379:methods*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D020547:Lateral Ventricles; D008279:Magnetic Resonance Imaging; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009414:Nerve Growth Factors / Q000235:genetics*; D009457:Neuroglia / Q000637:transplantation*; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D010215:Papio; D020734:Parkinsonian Disorders / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D020127:Recovery of Function / Q000187:drug effects; D013378:Substantia Nigra / Q000473:pathology; D014055:Tomography, Emission-Computed; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D002214:Capsules; D005462:Fluorine Radioisotopes; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D014446:Tyrosine 3-Monooxygenase