Protein biomarker indicators of neurological injury and/or disease and methods of use thereof
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Publication Number
US-11988676-B2
Publication Date
2024-05-21
Expiration Date
Abstract
Methods, compositions and kits useful in the detection, assessment, diagnosis, prognosis and/or treatment of neurological injury or disease or brain injury, such as traumatic brain injury (TBI), are provided in which certain newly discovered protein biomarkers are detected in a biological sample of a subject undergoing testing or evaluation. The methods allow for detection of changes in levels, amounts, or concentrations of the protein biomarkers in a subject compared with those of controls. Detection of the protein biomarkers, and/or levels thereof, provides an indication of biological and biochemical events, e.g., at a cellular level, that are occurring in the subject who is undergoing testing or analysis for the neurological injury or brain injury.
Core Innovation
The invention provides protein biomarker panels for detecting, diagnosing, prognosing, assessing, and monitoring neurological injury, particularly traumatic brain injury (TBI), including mild traumatic brain injury (mTBI) and concussion. The panel comprises two or more protein biomarkers and fragments, including von Willebrand Factor (vWF) and Astrotactin 2 (ASTN2), with biomarker detection based on measuring levels, amounts, concentrations, patterns, ratios, and post-translationally modified forms in a biofluid sample.
The biomarkers are measured in biofluids obtained from a subject having, or suspected of having, traumatic brain injury. The biofluid sample includes blood, serum, plasma, cerebrospinal fluid (CSF), saliva, urine, and other biofluids, and detection includes immunoassays such as ELISA, immunoblot, immunoprecipitation, multiplex assays, and mass spectrometry such as SRM/MRM, MALDI-TOF, and SELDI, including detection of autoantibodies to biomarker antigens.
The invention further uses biomarker trends and patterns for therapy effectiveness and for risk stratification regarding post-TBI outcomes. Post-TBI outcomes explicitly include seizures, depression, PTSD, sleep disorders, headache, chronic pain, and cognitive and oculomotor and balance problems, and the document additionally describes kit and composition embodiments, including substrates with immobilized binding agents and ELISA and immunochromatography formats.
Claims Coverage
The independent claim set centers on detecting two or more protein biomarkers, including vWF and ASTN2, in a biofluid sample from a subject having or suspected of having traumatic brain injury, using an assay or mass spectrometry. The claim coverage includes 6 inventive features.
Detecting vWF and ASTN2 in a traumatic brain injury biofluid sample
Detecting von Willebrand Factor (vWF) and Astrotactin 2 (ASTN2) in a biofluid sample by an assay or mass spectrometry.
Expanded protein biomarker panel
Detecting additional protein biomarkers selected from synaptogenesis proteins, innate immunity proteins, metabolism proteins, and inflammation proteins.
Assay modality selection for vWF and ASTN2
Detecting vWF and ASTN2 using an assay selected from immunoassay, immunoblot assay, immunoprecipitation assay, immunostaining method, quantitative assay, immunofluorescent assay, or chemiluminescence assay.
Reference level or pattern comparison for risk
Measuring vWF and ASTN2 levels in a biofluid sample and comparing the results to predefined reference levels or patterns linked to different risks of developing one or more particular brain injury outcomes.
Threshold-based therapy trigger based on vWF and ASTN2 expression
Measuring vWF and ASTN2 levels in a biofluid sample and administer a therapy to treat a traumatic brain injury when the measured levels are above or below predetermined expression thresholds relative to specified control groups.
Therapy directed to enumerated post-tbi conditions
Administering a therapy to treat a neurological or brain injury using one or more post-traumatic brain injury (TBI) treatments targeting seizures, depression, anxiety, PTSD, sleep disorders, headache, chronic pain, oculomotor deficits, attention and cognitive defects, and balance and gait problems.
Overall claim coverage is anchored by assaying or mass spectrometry detection of vWF and ASTN2 from a traumatic brain injury biofluid sample, with dependent claims expanding the biomarker panel, specifying assay modalities, comparing measured levels to reference levels or patterns for risk categories, and enabling threshold-based therapy administration targeted to enumerated post-TBI conditions.
Stated Advantages
Enables detecting, diagnosing, prognosing, assessing, and monitoring neurological injury, particularly traumatic brain injury (TBI).
Supports therapy effectiveness assessment using biomarker trends.
Enables risk stratification for post-TBI outcomes such as seizures, depression, PTSD, sleep disorders, headache, chronic pain, cognitive/oculomotor/balance problems.
Documented Applications
Detection/diagnosis/prognosis/assessment/monitoring of neurological injury, particularly traumatic brain injury (TBI), including mTBI and concussion.
Assessing therapy effectiveness using biomarker trends.
Risk stratification for post-TBI outcomes including seizures, depression, PTSD, sleep disorders, headache, chronic pain, and cognitive/oculomotor/balance problems.
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