Parkinson disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons. Current therapies provide symptomatic treatment only and thus fail to prevent the process of neurodegeneration. Recently, it has been reported that neurotrophic factors could support the survival and enhance the function of dopaminergic neurons. Thus, gene therapy using neurotrophic factors has become the center of interest. From this viewpoint, we focused on hepatocyte growth factor (HGF) as a novel neurotrophic and angiogenic growth factor. In this study, we examined the effects of over-expression of HGF on clinical symptoms induced in a monkey model of PD, aiming toward human gene therapy. Stereotaxic transfection of naked plasmid DNA encoding human HGF cDNA into the striatum resulted in significant prevention of behavioral, immunohistochemical, HPLC and PET scan findings. Overall, the present study demonstrated that over-expression of HGF prevented neuronal death in a PD primate model, providing a potential novel therapy for PD.