The goal of this project is to find drugs that target alpha-synuclein, a key protein in Parkinson's disease (PD). We will design and test second-generation antisense oligonucleotides (ASOs), man-made molecules that destroy mRNA, the template from which a protein is built. Treatment with ASO molecules is expected to decrease the production of alpha-synuclein in the long term and prevent its abnormal buildup and spreading in PD.
We hypothesize that by directly and chronically modifying the alpha-synuclein mRNA, we can decrease the buildup of alpha-synuclein in people with PD in the long term.
We will design and develop ASOs that modify the production of alpha-synuclein mRNA to make it least able to serve as a template for the protein. Initially, the validity and functionality of the designed ASOs will be tested in human cells that produce alpha-synuclein. The most efficient ASOs will then be tested in pre-clinical models to assess the reduction of alpha-synuclein levels in these models.
Impact on Diagnosis/Treatment of Parkinson's disease:
This study is designed to provide a proof that ASOs can be used to treat diseases linked to alpha-synuclein.
Next Steps for Development:
Following successful completion of the study, we will conduct further pre-clinical studies required to safely assess ASOs' potential for becoming candidate drugs for Parkinson's disease.