This study reports proof of concept for administering compacted DNA nanoparticles (DNPs) intracerebrally as a means to protect against neurotoxin-induced neurodegeneration of dopamine (DA) neurons. In this study we used DNPs that encoded for human glial cell line-derived neurotrophic factor (hGDNF); GDNF is a potent neurotrophic factor for DA neurons. Intracerebral injections of DNPs into the striatum and/or substantia nigra were performed 1 week before treatment with a neurotoxin. We observed that the number of surviving DA cells, the density of DA fiber terminals and recovery of motor function were greater in animals injected with GDNF-encoding DNPs than in control animals receiving DNPs encoding for an inert reporter gene. The results of these studies are one of the first to demonstrate that a non-viral, synthetic nanoparticle can be used to deliver therapeutic genes to cells in the brain as a means to protect cells against neurotoxin-induced neurodegeneration.
Keywords: Gene therapy; Glial cell line-derived neurotrophic factor (GDNF); Lysine polymer; Parkinson's disease; Plasmid DNA.
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