Protein biomarker indicators of neurological injury and/or disease and methods of use thereof

Inventors

VAN METER, Timothy E.

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 patent relates to assessing whether a therapy or treatment regimen for a neurological injury or brain injury is effective in a subject. The approach is based on quantitatively measuring the levels of one or more protein biomarkers, or fragments thereof, in a biological sample obtained at a first time point prior to initiation of the therapy or treatment regimen, and then at a second time point after initiation. The one or more protein biomarkers or fragments thereof comprise Astrotactin 2 (ASTN2).

Effectiveness is determined by comparing the measured biomarker levels at the first time point and the second time point. Treatment is ceased when the measured levels of the one or more protein biomarkers, or fragments thereof, are decreased or trending to normal levels at the second time point compared with the first time point, and treatment is continued when the measured levels are increased or trending to abnormal levels at the second time point compared with the first time point.

The patent further includes detection of protein biomarkers or fragments thereof in a biofluid sample from a subject having, or suspected of having, a neurological injury or brain injury. This detection comprises obtaining the biofluid sample and detecting Astrotactin 2 (ASTN2) in the biofluid sample by an assay or mass spectrometry.

Claims Coverage

The provided partial content contains two independent claims, together covering therapy effectiveness assessment based on ASTN2-containing protein biomarker changes across two time points and detecting ASTN2 in a biofluid sample from a subject with, or suspected of having, a neurological injury or brain injury. The inventive features focus on biomarker composition including ASTN2 and on decision rules or detection modalities tied to those measurements.

Claim coverage is centered on ASTN2 as a required protein biomarker. One independent claim uses quantitative comparison of biomarker levels at first and second time points to define whether treatment is ceased or continued based on decreased or trending-to-normal versus increased or trending-to-abnormal levels. The other independent claim focuses on detecting ASTN2 in a biofluid sample using an assay or mass spectrometry for subjects having, or suspected of having, a neurological injury or brain injury.

Stated Advantages

Documented Applications