Objective/Rationale:
This proposal seeks to develop a novel therapy that can slow the progression of Parkinson’s disease (PD) by optimizing chemical compounds that can decrease levels of alpha synuclein in the brain.
Project Description:
Neurodegenerative diseases are characterized by the accumulation in cells of damaged and misfolded proteins that form toxic aggregates, ultimately leading to cell death. Our strategy is to reduce these toxic proteins in cells by accelerating the body’s intrinsic ability to recognize and eliminate toxic proteins. Proteostasis Therapeutics, Inc. has identified novel chemical molecules that function by enhancing the activity of an intracellular protein complex called the proteasome, which is the primary site for the selective degradation of misfolded proteins in mammalian cells. We hypothesize that lowering a misfolded protein in cells, specifically alpha synuclein, will lessen its tendency to aggregate, reduce cellular toxicity, and extend cell survival. The aim of the project is to develop a chemical compound that can be tested in the clinic for its ability to slow the clinical progression of PD.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
This project has the potential to identify a novel treatment for PD. The project goal is to identify chemical compounds that lower the levels of the alpha synuclein protein in cells. These chemicals will be designed to be given in a pill form. If successful, the potential therapy will eventually be tested in patients for its ability to safely slow the progressive worsening of the symptoms of PD.
Anticipated Outcome:
At the completion of this study, we will have optimized chemical compounds with favorable drug-like properties that can lower alpha synuclein in cell models, brain slices, and in vivo. If successful, this will lead to the development of novel drug candidates that can be tested in patients for their ability to safely slow the progression of PD.