Parkinson's disease (PD) is a neurodegenerative disease characterized by the progressive loss of nigral dopaminergic neurons. Although symptomatic therapies to substitute for the missing neurotransmitter dopamine are efficient at the early stages of the disease, the goal is to find alternative therapies which could protect dopaminergic neurons from the degenerative process. We have used two distinct gene therapy approaches to deliver the neuroprotective molecule glial cell line-derived neurotrophic factor (GDNF) in animal models of the disease: (i) an encapsulated genetically engineered cell line releasing GDNF (ex vivo gene therapy); and (ii) a lentiviral vector encoding the GDNF gene (in vivo gene therapy). Both approaches allowed protection of nigral dopaminergic neurons against lesion-induced cell death in rodent as well as monkey models of PD. Behavioral symptoms were also ameliorated in these animals. In addition, co-transplantation of embryonic dopaminergic neuronal grafts and a GDNF-releasing capsule allowed improvement of graft survival and differentiation, thereby accelerating behavioral recovery. These results should lead to clinical application in the near future