A Long-Lasting Intranasal Gene Therapy Approach for Parkinson’s Disease

Research Category: Health Sciences
Presenter: Amirah Aly
PI: Barbara Waszczak

We have developed the first intranasal gene therapy approach with the potential to stop the progression of Parkinson’s disease (PD), and possibly reverse 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.  We have previously shown that our DNA NPs, developed by Copernicus Therapeutics, Inc., transfect pericytes, which are cells that enwrap blood vessels throughout the brain.

The goal of our current study was to determine the duration of protein expression after intranasal administration of these DNA NPs. Our findings indicated that protein levels were highest at one week after intranasal administration, and persisted over at least 6 months. Protein expression was elevated throughout the brain, including in the brain regions involved in PD. These studies reinforce the intranasal delivery of these NPs as a non-invasive, long-lasting means of gene therapy for PD and other CNS disorders.