US 2026/0219283 A1 · A DUPLEX ELECTROCHEMILUMINESCENCE IMMUNOASSAY FOR TOTAL A-SYNUCLEIN AND PS129-A-SYNUCLEIN

Abstract

Synucleinopathies are a group of neurodegenerative diseases including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). These diseases are characterized by the aggregation and deposition of α-synuclein (α-syn) in Lewy bodies (LBs) in PD and DLB or as glial cytoplasmic inclusions in MSA. In healthy brains, only ~4% of α-syn is phosphorylated at Ser129 (pS129-α-syn), whereas >90% pS129-α-syn may be found in LBs. Embodiments of the invention include a duplex assay for both total α-synuclein and pS129-α-synuclein, which allows measuring both analytes in the same sample, leading to substantial saving in sample volume. The assays can be widely used in methods for detecting pS129-α-syn in biomedical studies including when only a limited volume of sample is available and high sensitivity is required, offering new opportunities for diagnostic biomarkers, monitoring disease progression, and quantifying outcome measures in clinical trials.

Claims20

Dependent claims

A method of measuring amounts of total α-synuclein and amounts of pS129-α-synuclein in a single sample comprising:

(a) combining the sample with:
a α-synuclein capture antibody and a α-synuclein detection antibody coupled to a detectable label;
and
a pS129-α-synuclein capture antibody and a pS129-α-synuclein detection antibody coupled to a detectable label;
wherein:
the α-synuclein capture antibody exhibits an affinity for α-synuclein greater than an affinity that the pS129-α-synuclein capture antibody exhibits for pS129-α-synuclein;
and
amounts of the pS129-α-synuclein capture antibody and the amounts of the α-synuclein capture antibody are selected to form a concentration ratio that compensates for the different affinities;
(b) allowing the α-synuclein capture antibody and the α-synuclein detection antibody to bind α-synuclein
(c) allowing the pS129-α-synuclein capture antibody and the pS129-α-synuclein detection antibody to bind pS129-α-synuclein;
(c) observing the presence of the detectable labels;
and
(d) correlating the observed detectable labels to concentrations of α-synuclein and pS129-α-synuclein in the sample;
such that amounts of total α-synuclein and amounts of pS129-α-synuclein in the single sample are measured.

11 more elements

Dependencies are inferred from the claim text.

A duplex electrochemiluminescence immunoassay for total a-synuclein and ps129-a-synuclein

Life of this patent

A duplex electrochemiluminescence immunoassay for total a-synuclein and ps129-a-synuclein

Life of this patent

Abstract

Claims20