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.
Keywords: Animals ; Capsules ; Dihydroxyphenylalanine/*analogs & derivatives/diagnostic use ; Fluorine Radioisotopes/diagnostic use ; Gene Therapy/*methods ; Glial Cell Line-Derived Neurotrophic Factor ; Lateral Ventricles ; Magnetic Resonance Imaging ; Male ; Motor Activity/drug effects ; Nerve Growth Factors/*genetics ; Neuroglia/*transplantation ; Neurons/enzymology/pathology ; Papio ; Parkinsonian Disorders/pathology/radionuclide imaging/*therapy ; Recovery of Function/drug effects ; Substantia Nigra/pathology ; Tomography ; Emission-Computed ; Tyrosine 3-Monooxygenase/metabolism
Research Associate Unit URA CEA CNRS 2210, Service Hospitalier Frederic Joliot, Orsay, France.
Record created on 2008-08-27, modified on 2016-08-08