Objective: To develop a sensitive, specific and consistent detection of a-SynO in biofluids to provide a reliable biomarker for disease diagnosis, progression, and a theranostic approach.

Background: Currently there are no diagnostic biomarker assays for Parkinson’s disease (PD) and other synucleinopathies based on biochemical analyses of biofluids (blood, CSF). Alpha-synuclein (a-Syn) is presumed to be the main pathological driver of PD. The assembly of oligomers of alpha-synuclein (a-SynO) represents a toxic gain of function for a-Syn and reportedly plays a central role in the neuropathophysiological changes leading to PD. We have developed a laser-based immunoassay and have previously demonstrated successful detection and quantitation of brain-derived biomarkers in biofluids from animals and humans with neurodegenerative diseases. This assay, termed RCA-SOFIA, involves linking an antigen-antibody complex to a nucleic acid which is then simultaneously amplified isothermally and fluorescently labelled followed by a fiberoptic detection scheme.

Method: (a) Study Design: (i) a-SynO assay development using the RCA-SOFIA platform and a commercially available, single molecule array (SIMOA) (homebrew) platform, (ii) Characterizing the analytical metrics associated with in vitro a-SynO detection, (iii) Validating RCA-SOFIA and SIMOA in vivo by detection of a-SynO in stratified PD (and control) patient blood.
(b) Subject Recruitment: Forty participants with PD (20 H&Y Stage I-II and 20 H&Y stage IV-V) are being recruited from two outpatient neurology clinics and age matched with controls.
(c) Statistical analysis: Collected variables will be tested for possible dependencies. Results will be analyzed for significance and outcomes will be compared for quantitative associations. Sensitivity and specificity will be computed and the effects will be compared by the area under the curve (AUC) of the Receiver Operating Characteristic (ROC) curve.

Results:
The study is on-going; preliminary results will be presented. ​

Conclusion:
PD diagnosis mainly relies on clinical symptoms which can be heterogeneous. A reliable prognostic biomarker can aid in predicting the response to treatments and function as outcome measures in clinical trials. The data obtained will be used to generate a power analysis for determining statistically relevant sample sizes for further studies.  ​​​​​​​

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MDS Abstracts - https://www.mdsabstracts.org/abstract/development-and-characterization-of-an-ultrasensitive-assay-platform-for-detection-of-pd-associated-alpha-synuclein-oligomers-in-human-blood/