Category: Assay Development and Screening

1296-B - Development of a Scintillation Proximity Assay for High Throughput Screening of Alpha Synuclein Aggregates

Monday, February 5, 2018
5:00 PM - 6:00 PM

Accumulation of aggregated alpha synuclein (aSYN) in the form of Lewy bodies is the pathological hallmark of Parkinson’s disease (PD).  In vivo imaging of the aSYN aggregates with a radiotracer will become a very useful tool for early PD diagnoses, tracking of disease progression and monitoring treatment efficacy. The objective is to develop a high-throughput screening (HTS) assay to identify small molecules that selectively bind to aSYN aggregates.  Conventional filtration binding assays are time consuming, labor intensive, and often low throughput making them a sub-optimal choice for large scale compound screening. We have developed a competitive binding assay amenable to HTS in a scintillation proximity assay (SPA) format. This 384-well SPA assay exhibits saturable, competitive binding specific to aSYN aggregates and robust assay metrics. The assay was used to screen an in-house library consisting of 260K compounds. The screen has yielded several new structural series to enable SAR and a potential path to develop a PET ligand for PD treatment and diagnoses.

Qifeng Yang

Senior Scientist
Merck & Co., Inc
Kenilworth, New Jersey

I have extensive research experiences in pharmaceutical industry in the fields of molecular biology, biochemistry, cell biology and immunology. I have been working on screening now and am interested in HTS and automation technology.