Methods and compositions for diagnosing brain injury or neurodegeneration
Inventors
SOREK, RACHEL • JAKOBI, KEREN • EDMONDS, DONNA
Assignees
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Publication Number
US-12038446-B2
Publication Date
2024-07-16
Expiration Date
Abstract
Methods and compositions for diagnosing brain injury, neurodegeneration; or a predisposition thereto, in a subject are provided. Particularly, the present invention relates to specific antigen antibody reactivities useful in diagnosing brain injury, neurodegeneration or a predisposition thereto, in a subject.
Core Innovation
The invention provides diagnostic methods, kits, and antigen probe set assays, including antigen probe sets/arrays and microarray/iChip formats, for identifying brain injury and neurodegeneration or predisposition to brain injury. The methods measure a subject antibody reactivity profile, including IgG and IgM, to brain-related antigens that include SEQ ID NOs 1-115 and variants, fragments, and post-translational modifications of the antigens.
Antibody reactivity patterns are compared to healthy controls or baseline samples, including monitoring a pre-existing state. The comparison supports diagnosing brain injury and neurodegeneration by determining whether measured signals show a pattern relative to the healthy control or baseline, and the profile is analyzed using learning and pattern recognition classifiers.
The disclosure further supports combined assessment using circulating autoantibodies together with brain injury biomarkers, including GFAP and other brain injury-associated proteins such as Synuclein beta (SNCB), MT3, NRGN, ICAM5, and BDNF, to assess injury status, subtype, severity, progression, or recovery. Example results describe differential autoantibody signals and classification performance, including ROC-based classification, correlations with GOSE outcomes, and differentiation of intracranial hemorrhage versus normal CT at early time points.
Claims Coverage
The provided independent claim includes four inventive features in combination: detecting SNCB, comparing it to a healthy control, diagnosing brain injury when SNCB is higher than the healthy control, and treating the diagnosed subject, with an additional requirement to detect GFAP at a higher level than in the healthy control before treatment.
Detecting SNCB and comparing to healthy control
Detect biomarker protein synuclein beta (SNCB) in a biological sample using an immunoassay, an antigen probe set assay, a microarray assay, a dipstick assay, or a chip assay; measure the level of SNCB relative to a healthy control.
Diagnosing brain injury when SNCB is higher than healthy control
Diagnose the subject as having or suspected of having brain injury when the level of SNCB measured is higher than the level in the healthy control.
Treating brain injury after diagnosis
Treat brain injury in the subject diagnosed as having or suspected of having brain injury.
Pre-treatment requirement: detecting GFAP higher than healthy control
Prior to treatment, further comprise detecting and measuring in the biological sample a level of glial fibrillary acidic protein (GFAP) that is higher than the level of GFAP in the healthy control.
The claim coverage centers on SNCB detection relative to a healthy control for diagnosis of brain injury, followed by treatment, with GFAP also required to be higher than in the healthy control before treatment. Related claim refinements specify assay formats, biomarker forms, sample types, and additional autoantibody measurements against specified proteins.
Stated Advantages
Supports diagnosing brain injury when SNCB is higher than in a healthy control.
Requires GFAP to be higher than in a healthy control prior to treatment.
Enables use of multiple assay formats for detecting biomarkers, including immunoassay, antigen probe set assay, microarray assay, dipstick assay, or chip assay.
Documented Applications
Diagnosing brain injury and neuroneurodegeneration or predisposition to brain injury by measuring antibody reactivity profiles (IgG and IgM) to brain-related antigens and comparing patterns to healthy controls or baseline samples.
Assessing injury status, subtype, severity, progression, or recovery using combined measurement of circulating autoantibodies and brain injury biomarkers including GFAP and other listed brain injury-associated proteins.
Differentiating intracranial hemorrhage versus normal CT at early time points using described classification outcomes and correlations.
Using biomarker and antibody profiles correlated with GOSE outcomes as described in example results.
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