Study Rationale:
Multiple lines of evidence suggest that alpha-synuclein gain-of-function is characteristic of Parkinson’s disease (PD). Reduction of alpha-synuclein expression represents a promising strategy for improving the motor and non-motor symptoms of the disease. Our proposed therapeutic, an orally bioavailable treatment, aims to reduce the progressive onset of Parkinson’s.
Hypothesis:
We hypothesize that compounds that reduce alpha-synuclein expression can be used as potential therapeutics for Parkinson’s.
Study Design:
We plan to use a novel alpha-synuclein cell line assay (laboratory test), which was previously developed though quantitative high throughput screening (assessment of biological or biochemical activity), to identify compounds that reduce alpha-synuclein expression. The most promising compounds will be evaluated for their ability to lower alpha-synuclein levels in neuronal cultures, as well as their ability to protect Parkinson’s disease fibroblasts (connective cell tissue) against natural toxins.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
We aim to identify the first class of drugs to lower alpha-synuclein expression, which could be developed into effective treatments for PD.
Next Steps for Development:
Future studies will test if the compounds identified in our study can lower neuronal alpha-synuclein expression levels in a pre-clinical model of PD. We will also study drug efficacy and oral bioavailability as additional steps toward developing a new treatment for Parkinson’s.