Study Rationale:
Gene therapy is one of the most promising tools for the treatment of Parkinson's disease (PD). We have developed a novel system to treat brain diseases using exosomes, which are small sacs of cellular material released by a cell. We modified exosomes to target the brain after injection into the blood stream, and we developed ways to insert into the exosome small hairpin RNA (shRNA) minicircles. These are chemical messengers that may decrease levels of the protein alpha-synuclein, believed to play a central role in PD. Using a laboratory model that mimics key features of PD, we demonstrated our therapy prevents the loss of brain cells, decreases pathology and avoids motor deficit.
Hypothesis:
We aim now to evaluate if our treatment is effective after the appearance of alpha-synuclein pathology, corresponding to the initial stage of PD.
Study Design:
This project will use the new gene therapy method that we have developed using shRNA minicircles loaded into exosomes to decrease levels of alpha-synuclein. We will treat the models after the development of alpha-synuclein pathology and confirm that our therapy halt Parkinson's disease progression.
Impact on Diagnosis/Treatment of Parkinson's disease:
The completion of this project will allow us to determine if exosomal delivery of gene therapy agents could halt or delay progression of Parkinson's disease in initial stages of the process. Consequently, it will pave the way for this technology to be further developed for clinical trials for Parkinson's disease.
Next Steps for Development:
We aim to develop this technology for human use. We will optimize a source of exosomes from the same patient to avoid problems associated with multiple dose treatments. Using cell and pre-clinical models, we will optimize this system and demonstrate its potential use in clinic.