Promising Outcomes of Original Grant: 100 words)
Synucleinopathies, including Parkinson's disease (PD), is a group of disorders affecting the central nervous system (CNS). These disorders share one key feature: clumping of protein alpha-synuclein in the brain. Toll-like receptors (TLRs) -- proteins on the surface of the cell that play a major role in immunity -- may be able to detect alpha-synuclein clumps and launch a harmful immune response. Blocking TLRs reduces this immune response; thus, blocking one of the TLRs, TLR2, may represent a therapeutic strategy to disrupt alpha-synuclein¬-mediated CNS inflammation and slow PD progression.
Objectives for Supplemental Investigation:
In this study, we will proceed with the pre-clinical development of the most promising TLR2-blocking drugs identified earlier. Specifically, we will continue to study these TLR2-blocking drugs to better understand how they travel throughout the body, how well they work in pre-clinical models and how safe they are. We will also search for the best process for production of these drugs.
Importance of This Research for the Development of a New PD Therapy:
Blocking of TLR2-mediated harmful immune response would serve as a novel therapeutic strategy for slowing PD progression. The data generated in the course of this study will help us decide whether these drugs hold sufficient promise as a potential therapeutic (reversing the course of disease) or disease-modifying (slowing or stopping disease progression) strategy for synucleinopathies.