Encapsulated GDNF-producing C2C12 cells for Parkinson's disease: a pre-clinical study in chronic MPTP-treated baboons.
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.
Kishima
Haruhiko
H
Research Associate Unit URA CEA CNRS 2210, Service Hospitalier Frédéric Joliot, Orsay, France.
Poyot
Thomas
T
Bloch
Jocelyne
J
Dauguet
Julien
J
Condé
Françoise
F
Dollé
Frédéric
F
Hinnen
Françoise
F
Pralong
William
W
Palfi
Stéphane
S
Déglon
Nicole
N
Aebischer
Patrick
P
Hantraye
Philippe
P
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
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