We have developed an intranasal gene therapy approach that may one day stop Parkinson’s disease (PD) in its tracks, preventing disease progression and possibly reversing its symptoms. Available drugs on the market alleviate symptoms of PD but do not get to the heart of the problem, which is the progressive loss of dopamine neurons. Our lab has found a way to harvest the potential of glial cell line-derived neurotrophic factor (GDNF) as a treatment for PD. GDNF is a protein that activates survival and growth-promoting pathways, protects dopamine neurons from injury, and restores their function. However, GDNF does not cross the blood-brain barrier (BBB), so its use would require surgical injection into the brain. We are investigating intranasal delivery of DNA nanoparticles (NPs) encoding GDNF as a way to bypass the BBB and allow the brain to continuously produce GDNF. Our NPs, developed by Copernicus Therapeutics, Inc., have been shown to transfect cells in brain resulting in long-term production of GDNF. The goal of these studies was to determine if intranasal administration leads to increased GDNF expression and protection of dopamine neurons in rat brain.
One week after intranasal administration, GDNF levels were significantly increased throughout the brain. The transfected cells were largely adjacent to capillaries, suggesting they may be pericytes. Most importantly, intranasal GDNF NPs provided significant neuroprotection of dopamine neurons in a standard rat model of PD. These results demonstrate that intranasal delivery of Copernicus’ NPs provides an effective and non-invasive means of GDNF gene therapy for PD.