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Funded Studies

Nanoparticle Gene Therapy for Parkinson's Disease

In this research project we will determine the feasibility of condensing plasmid DNA into nanoparticles and using these nanoparticles to deliver their payload into cells of the central nervous system as a non-viral gene therapy technique. The condensed DNA nanoparticles will be implanted directly into the brains of rodent models of PD. We will focus on the ability of these nanoparticles to enter brain cells and induce transgene expression of a gene encoding for a neurotrophic factor that is known to be beneficial for the survival of the cells.

We are testing this technique as a means to halt the degeneration of dopamine neurons in rodent models of Parkinson's disease. DNA condensed into nanoparticles has been shown to effectively transfect non-dividing cells, including growth-arrested neuroblastoma cells, and may be a viable vehicle to deliver neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF), to dopamine neurons.

The overall objective of these studies will be to determine whether recombinant plasmid DNA encoding for GDNF and compacted into nanoparticles can be safely delivered to the brain and successfully transduce brain cells to overexpress GDNF and prevent the neurodegeneration of dopamine neurons in an animal model of Parkinson's disease.

Final Outcome

We tested various GDNF plasmids and compared GDNF DNA incorporating sequences. We reported the results from a dose?response study that used four different pGDNF expression plasmids that were compacted into nanoparticles and then injected in the striatum. Protein analysis for GDNF in striatal tissue samples were determined one week later and it was determined that a plasmid encoding for natural GDNF provided the best transgene expression (of note, a different variant is used in most preclinical studies) resulting in GDNF protein levels that were more than 400 perecent higher than baseline levels for at least an eight-week period.

We received supplemental funding to test the optimized plasmid from the dose?response study in a longitudinal study of GDNF overexpression in the striatum; if necessary, a proprietary element that confers long term expression of other transgenes will be included in the plasmid design.

The ultimate goal of our studies is to design a GDNF expression plasmid that can be compacted into nanoparticles, injected into the brain, and then produce long?term transgene expression of GDNF in the striatum.

In addition to the supplemental funding we received from MJFF, our team received follow-on funding in the form of an R21 grant from NIH in August 2009. The goals of this award, titled “Targeted DNA Nanoparticles in Brain,” are to modify DNA nanoparticles so they cross the blood brain barrier and target neurons. We did not, however, propose to test these modified particles in a pre-clinical model of neurodegeneration.


  • David Yurek, PhD

    Lexington, KY United States

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