Study Rationale:
The hypothesis that misfolded alpha-synuclein (a protein associated with Parkinson's) aggregates (clumps) move from neuron-to-neuron is gaining widespread acceptance as a central mechanism in the development of Parkinson's disease (PD). Therapies designed to stop this spreading point towards a novel therapeutic route for preventing the development of PD.
Hypothesis:
With the development of a small molecule that stops the spreading of alpha-synuclein aggregates, we propose to identify the target(s) of this compound, with the goal of understanding how it blocks alpha-synuclein spreading. These targets can then be explored to develop additional compounds.
Study Design:
As our small molecule was identified through screening, the cellular target(s) of this compound are unknown. Thus, our goal for this study is to identify these target(s) through a combination of complimentary genetic and proteomic (study of a set of proteins) approaches. This will allow us to narrow down the list of potential target genes for testing and validation as drug targets of our small molecule. We are confident that results from these distinct but complementary approaches will help inform each other, thereby guiding the direction of the work and increasing our likelihood of success in identifying the target(s) of our small molecule.
Impact on Diagnosis/Treatment of Parkinson's disease:
This proposal will allow us to identify target(s) of our small molecule that can then be explored for future efforts in the development of additional compounds for the treatment of Parkinson's.
Next Steps for Development:
Our goal is to move our compound and future analogues into Phase 1 trials. Such a trial, in partnership with the Centre for Drug Research and Development and its industry partners, can be conducted at the Montreal Neurological Institute and Hospital through its clinical research unit, which has ample experience in conducting such trials.