The Open Gene Therapy Journal

2009, 2 : 38-44
Published online 2009 July 23. DOI: 10.2174/1875037000902010038
Publisher ID: TOGTJ-2-38

Injection of HGF Plasmid cDNA to Prevent Manifestation of Parkinson Disease: A Preclinical Study using a Primate Model

Hiromi Koike , Akihiko Ishida , Takuya Hayashi , Munehisa Shimamura , Shinya Mizuno , Toshikazu Nakamura , Hidehiro Iida , Toshio Ogihara , Yasufumi Kaneda and Ryuichi Morishita
Division of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita 565-0871, Japan

ABSTRACT

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.

Keywords:

Gene therapy, naked DNA, HGF, parkinson disease, neurotrophic factor.