Methods for aiding in the diagnosis and determination of the extent of traumatic brain injury in a human subject using the early biomarker ubiquitin carboxy-terminal hydrolase L1
Inventors
McQuiston, Beth • Rogers, Justin • Datwyler, Saul • Marino, Jaime
Assignees
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Publication Number
US-12163958-B2
Publication Date
2024-12-10
Expiration Date
Abstract
Disclosed herein are methods that aid in the diagnosis and evaluation of a human subject that has sustained or may have sustained an injury to the head, such as mild or moderate to severe traumatic brain injury (TBI), using an early biomarker, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1). Also disclosed here are methods that aid in determining whether a human subject that has sustained an injury or may have sustained to the head would benefit from and thus receive a head computerized tomography (CT) scan based on the levels of UCH-L1. These methods involve detecting levels and changes in levels of UCH-L1 in one or more samples taken from a human subject at time points within 24 hours after the subject has sustained or may have sustained an injury to the head.
Core Innovation
The patent describes measuring ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) in samples obtained from a human subject after a head injury or suspected head injury. The method uses at least a first sample and a second sample collected at different time points, and compares the measured UCH-L1 level in the second sample to the first sample using fold-change relationships to classify traumatic brain injury severity, including mild TBI and moderate to severe TBI.
The described criteria include statistically significant increase, statistically significant decrease, and no statistically significant change, as well as absolute level thresholds. Example timing windows include a first sample within about 0-24 hours or about 0-12 hours of suspected injury and a second sample about 3-6 hours later, and the sample types include whole blood, serum, plasma, or cerebrospinal fluid.
The method also describes head CT scan decisions based on UCH-L1 reference levels and/or statistically significant absolute or fold changes. Assay formats are described as not critical, and immunoassay, clinical chemistry, single molecule detection, lateral flow assay, and point-of-care assay concepts are included.
Claims Coverage
The consolidated claims coverage includes three independent inventive frameworks. These frameworks cover paired UCH-L1 fold-change classification with differential treatment, single-sample UCH-L1 absolute level classification with differential treatment, and paired UCH-L1 fold-change classification with a head CT scan trigger and treatment. Across the independent claims, the inventive features center on UCH-L1 measurement, threshold-based separation of mild TBI versus moderate to severe TBI, and associated care actions.
Paired UCH-L1 fold-change guides mild versus moderate-to-severe treatment
Performing an assay for ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) in at least a first sample and a second sample from a human subject after a head injury or suspected head injury, comparing the second sample to the first sample using fold-change, and treating the subject for a moderate to severe TBI when the fold-change is greater than or equal to about 0.73, or for a mild TBI when the fold-change is less than about 0.73.
Absolute UCH-L1 level guides mild versus moderate-to-severe treatment
Performing an assay for ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) in at least a first sample from a human subject after a head injury or suspected head injury, and treating the subject for a moderate to severe TBI when the UCH-L1 level is greater than or equal to about 350 pg/mL, or for a mild TBI when the level is less than about 350 pg/mL.
UCH-L1 fold-change triggers performing a head CT scan and supports treatment
Performing an assay for ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) in at least a first sample and a second sample from a human subject after a head injury or suspected head injury, and performing a head CT scan on the subject when the second sample exhibits a fold-change of less than about 1.5 compared to the first sample, followed by treating the subject for a moderate to severe TBI or for a mild TBI.
The claims collectively center on UCH-L1-based severity classification and treatment using either paired-sample fold-change thresholds, including about 0.73 and about 1.5, or a single-sample absolute level threshold of about 350 pg/mL. One independent framework additionally requires a head CT scan triggered by the UCH-L1 fold-change condition.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating a subject for moderate to severe traumatic brain injury (TBI) or for a mild TBI after a head injury or suspected head injury using UCH-L1 measurements and fold-change or absolute UCH-L1 thresholds.
Performing a head CT scan when the UCH-L1 fold-change is below about 1.5 and using the CT scan in connection with suspecting traumatic brain injury and monitoring the subject.
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