Neurobiology of Disease (Jul 2004)
Encapsulated GDNF-producing C2C12 cells for Parkinson's disease: a pre-clinical study in chronic MPTP-treated baboons
- Haruhiko Kishima,
- Thomas Poyot,
- Jocelyne Bloch,
- Julien Dauguet,
- Françoise Condé,
- Frédéric Dollé,
- Françoise Hinnen,
- William Pralong,
- Stéphane Palfi,
- Nicole Déglon,
- Patrick Aebischer,
- Philippe Hantraye
Affiliations
- Haruhiko Kishima
- Research Associate Unit URA CEA CNRS 2210, Service Hospitalier Frédéric Joliot, Orsay, France; Swiss Federal Institute of Technology Lausanne (EPFL), Institute of Neuroscience, Lausanne, Switzerland; Isotopic Imaging, Biochemical and Pharmacological Unit (UI2BP), Department of Medical Research, Service Hospitalier Frédéric Joliot, Orsay, France; Neurosurgery Service, CHU Henri Mondor Hospital, AP-HP, 94010 Créteil, France
- Thomas Poyot
- Research Associate Unit URA CEA CNRS 2210, Service Hospitalier Frédéric Joliot, Orsay, France; Swiss Federal Institute of Technology Lausanne (EPFL), Institute of Neuroscience, Lausanne, Switzerland; Isotopic Imaging, Biochemical and Pharmacological Unit (UI2BP), Department of Medical Research, Service Hospitalier Frédéric Joliot, Orsay, France; Neurosurgery Service, CHU Henri Mondor Hospital, AP-HP, 94010 Créteil, France
- Jocelyne Bloch
- Research Associate Unit URA CEA CNRS 2210, Service Hospitalier Frédéric Joliot, Orsay, France; Swiss Federal Institute of Technology Lausanne (EPFL), Institute of Neuroscience, Lausanne, Switzerland; Isotopic Imaging, Biochemical and Pharmacological Unit (UI2BP), Department of Medical Research, Service Hospitalier Frédéric Joliot, Orsay, France; Neurosurgery Service, CHU Henri Mondor Hospital, AP-HP, 94010 Créteil, France
- Julien Dauguet
- Research Associate Unit URA CEA CNRS 2210, Service Hospitalier Frédéric Joliot, Orsay, France; Swiss Federal Institute of Technology Lausanne (EPFL), Institute of Neuroscience, Lausanne, Switzerland; Isotopic Imaging, Biochemical and Pharmacological Unit (UI2BP), Department of Medical Research, Service Hospitalier Frédéric Joliot, Orsay, France; Neurosurgery Service, CHU Henri Mondor Hospital, AP-HP, 94010 Créteil, France
- Françoise Condé
- Research Associate Unit URA CEA CNRS 2210, Service Hospitalier Frédéric Joliot, Orsay, France; Swiss Federal Institute of Technology Lausanne (EPFL), Institute of Neuroscience, Lausanne, Switzerland; Isotopic Imaging, Biochemical and Pharmacological Unit (UI2BP), Department of Medical Research, Service Hospitalier Frédéric Joliot, Orsay, France; Neurosurgery Service, CHU Henri Mondor Hospital, AP-HP, 94010 Créteil, France
- Frédéric Dollé
- Research Associate Unit URA CEA CNRS 2210, Service Hospitalier Frédéric Joliot, Orsay, France; Swiss Federal Institute of Technology Lausanne (EPFL), Institute of Neuroscience, Lausanne, Switzerland; Isotopic Imaging, Biochemical and Pharmacological Unit (UI2BP), Department of Medical Research, Service Hospitalier Frédéric Joliot, Orsay, France; Neurosurgery Service, CHU Henri Mondor Hospital, AP-HP, 94010 Créteil, France
- Françoise Hinnen
- Research Associate Unit URA CEA CNRS 2210, Service Hospitalier Frédéric Joliot, Orsay, France; Swiss Federal Institute of Technology Lausanne (EPFL), Institute of Neuroscience, Lausanne, Switzerland; Isotopic Imaging, Biochemical and Pharmacological Unit (UI2BP), Department of Medical Research, Service Hospitalier Frédéric Joliot, Orsay, France; Neurosurgery Service, CHU Henri Mondor Hospital, AP-HP, 94010 Créteil, France
- William Pralong
- Research Associate Unit URA CEA CNRS 2210, Service Hospitalier Frédéric Joliot, Orsay, France; Swiss Federal Institute of Technology Lausanne (EPFL), Institute of Neuroscience, Lausanne, Switzerland; Isotopic Imaging, Biochemical and Pharmacological Unit (UI2BP), Department of Medical Research, Service Hospitalier Frédéric Joliot, Orsay, France; Neurosurgery Service, CHU Henri Mondor Hospital, AP-HP, 94010 Créteil, France
- Stéphane Palfi
- Research Associate Unit URA CEA CNRS 2210, Service Hospitalier Frédéric Joliot, Orsay, France; Swiss Federal Institute of Technology Lausanne (EPFL), Institute of Neuroscience, Lausanne, Switzerland; Isotopic Imaging, Biochemical and Pharmacological Unit (UI2BP), Department of Medical Research, Service Hospitalier Frédéric Joliot, Orsay, France; Neurosurgery Service, CHU Henri Mondor Hospital, AP-HP, 94010 Créteil, France
- Nicole Déglon
- Research Associate Unit URA CEA CNRS 2210, Service Hospitalier Frédéric Joliot, Orsay, France; Swiss Federal Institute of Technology Lausanne (EPFL), Institute of Neuroscience, Lausanne, Switzerland; Isotopic Imaging, Biochemical and Pharmacological Unit (UI2BP), Department of Medical Research, Service Hospitalier Frédéric Joliot, Orsay, France; Neurosurgery Service, CHU Henri Mondor Hospital, AP-HP, 94010 Créteil, France
- Patrick Aebischer
- Research Associate Unit URA CEA CNRS 2210, Service Hospitalier Frédéric Joliot, Orsay, France; Swiss Federal Institute of Technology Lausanne (EPFL), Institute of Neuroscience, Lausanne, Switzerland; Isotopic Imaging, Biochemical and Pharmacological Unit (UI2BP), Department of Medical Research, Service Hospitalier Frédéric Joliot, Orsay, France; Neurosurgery Service, CHU Henri Mondor Hospital, AP-HP, 94010 Créteil, France
- Philippe Hantraye
- Research Associate Unit URA CEA CNRS 2210, Service Hospitalier Frédéric Joliot, Orsay, France; Swiss Federal Institute of Technology Lausanne (EPFL), Institute of Neuroscience, Lausanne, Switzerland; Isotopic Imaging, Biochemical and Pharmacological Unit (UI2BP), Department of Medical Research, Service Hospitalier Frédéric Joliot, Orsay, France; Neurosurgery Service, CHU Henri Mondor Hospital, AP-HP, 94010 Créteil, France
- Journal volume & issue
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Vol. 16,
no. 2
pp. 428 – 439
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.
