CNS gene transfer could provide new approaches to the modelling of neurodegenerative
diseases and devising potential therapies. One such disorder is Parkinson’s
disease (PD), in which dysfunction of several different metabolic processes
has been implicated. Here we review the literature on gene transfer systems
based on herpes simplex virus type 1 (HSV-1) and non-viral
polyethyleneimine (PEI) and calcium phosphate nanoparticle methods. We also
assess the usefulness of various CNS gene delivery methods and present some
of our own data to exemplify such usefulness. Our data result from vectors
stereotaxically introduced to the substantia nigra (SN) of adult rats and evaluated
1 week and/or 1 month post injection using histochemical methods to assess
recombinant ß-galactosidase enzyme activity. Gene transfer using PEI or calcium
phosphate-mediated transfections was observed for both methods and PEI was
comparable to that of HSV-1 amplicon. Our data show that the amplicon delivery
was markedly increased when packaged with a helper virus and was similar
to the expression profile achieved with a full-size replication-defective HSV-1
recombinant (8117/43). We also examine whether PEI or HSV-1 amplicon-mediated
gene transfer could facilitate assessment of the biological effects induced
by a dominant negative FGF receptor-1 mutant to model the reduced FGF signalling
thought to occur in Parkinson’s disease