Exogenous expression of hepatocyte growth factor (HGF) in rat striatum by naked plasmid DNA

Prevention of onset of Parkinson’s disease by in vivo gene transfer of human hepatocyte growth factor in rodent model: a model of gene therapy for Parkinson’s disease

“…32 To overcome this problem, the injection site was localized using a streotactic technique with a high dosage. Consistent with the previous report, 33 we detected the exogenous protein of human HGF in the striatum. Interestingly, exogenous HGF was mainly expressed in reactive astrocytes, and that c-met was also expressed in the injection site.…”

“…Interestingly, exogenous HGF was mainly expressed in reactive astrocytes, and that c-met was also expressed in the injection site. 33 Overall, the present study demonstrated that gene transfer of HGF protects dopaminergic neurons from the toxicity induced by 6-OHDA, resulting in prevention of the onset of PD. As no significant loss of body weight or histological change was observed throughout the experimental period, these data clearly demonstrate the clinical utility of a therapeutic strategy based upon plasmid DNA-mediated transfer.…”

“…23 As naked plasmid DNA is very safe and easy to handle as compared to viral vectors, intramuscular injection of naked plasmid DNA of angiogenic growth factors such as VEGF and HGF has been widely used clinically for the treatment of ischemic cardiovascular disease. [29][30][31] Some researchers have tried to apply direct injection of naked plasmid DNA into the brain; 32,33 however, the transfection efficiency was quite low. 32 To overcome this problem, the injection site was localized using a streotactic technique with a high dosage.…”

Development of efficient plasmid DNA transfer into adult rat central nervous system using microbubble-enhanced ultrasound

“…11 Since glial cells are important for neuronal survival via the secretion of various neurotrophic factors such as fibroblast growth factor (FGF) and hepatocyte growth factor (HGF), 24 gene transfer of neurotrophic factors to glial cells might promote survival of neurons in neurodegenerative diseases such as Parkinson's disease. Alternatively, as a recent report showed that delivery of recombinant GDNF directly into the putamen of five Parkinson's disease patients in a phase I safety trial produced functional improvement, 25 gene transfer might allow long-term production of neuroprotective growth factors, thus resulting in a better outcome.…”

“…8,9 Although some researchers have tried to apply direct injection of naked plasmid DNA into the brain, 10,11 the transfection efficiency was quite low 10 and a large amount of naked plasmid DNA was required to produce the target protein. 11 Recently, ultrasound-mediated gene transfer has been reported to augment the transfection efficiency and facilitate local gene expression. 12 Interestingly, gene transfer into the fetal central nervous system was successfully achieved by intrauterine injection with microbubble-enhanced ultrasound.…”