Methods for aiding in the hyperacute diagnosis and determination of traumatic brain injury in a human subject using early biomarkers
Inventors
McQuiston, Beth • Rogers, Justin • Datwyler, Saul • Marino, Jaime
Assignees
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Publication Number
US-12099069-B2
Publication Date
2024-09-24
Expiration Date
Abstract
Disclosed herein are methods that aid in the hyperacute diagnosis and evaluation of a human subject that has sustained or may have sustained an injury to the head, such as mild or moderate, severe, or moderate to severe traumatic brain injury (TBI), using an early biomarker, such as ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) glial fibrillary acidic protein (GFAP), or a combination thereof. Also disclosed here are methods that aid in the hyperacute determination of 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 of early biomarker, such as ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) glial fibrillary acidic protein (GFAP), or a combination thereof, in samples taken from a human subject at a time point within about 2 hours, such as about 10, 12, or 20 minutes, after the subject has sustained or may have sustained an injury to the head.
Core Innovation
The invention provides hyperacute diagnosis and triage of traumatic brain injury (TBI) by measuring early biomarkers in a human sample obtained within about 2 hours after an actual or suspected injury to the head. The biomarkers include ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and/or glial fibrillary acidic protein (GFAP), measured in whole blood, serum, plasma, and cerebrospinal fluid (CSF). The approach classifies injury severity using biomarker reference levels and cutoff thresholds.
The method correlates measured GFAP and UCH-L1 levels to TBI severity categories, including mild versus moderate, severe, or moderate to severe TBI. In at least some embodiments, GFAP greater than about 9.0 pg/mL indicates moderate, severe, or moderate to severe TBI, while GFAP less than about 9.0 pg/mL indicates mild TBI. Likewise, UCH-L1 greater than about 73.5 pg/mL indicates moderate, severe, or moderate to severe TBI, while UCH-L1 less than about 73.5 pg/mL indicates mild TBI.
The invention also links biomarker levels to head computerized tomography (CT) triage and treatment decisions. A head CT scan is performed when biomarker levels exceed defined reference or cutoff levels, including when GFAP is greater than about 9.0 pg/mL and/or UCH-L1 is greater than about 73.5 pg/mL.
Claims Coverage
Two independent claims are presented. Both recite assays for UCH-L1 and/or GFAP in specific human sample types obtained within about 2 hours, and both use quantitative biomarker thresholds to determine TBI severity; one independent claim additionally recites a CT scan decision based on those levels.
Hyperacute biomarker assay for TBI severity using UCH-L1 and/or GFAP
Performing at least one assay for ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), or a combination thereof in at least one sample that is whole blood, serum, plasma, or cerebrospinal fluid obtained from a human subject within about 2 hours after an actual or suspected injury to the head.
Biomarker-threshold-based treatment selection for mild versus moderate/severe TBI
Treating the subject for a moderate, severe, or moderate to severe traumatic brain injury (TBI) when the level of GFAP is greater than about 9.0 pg/mL, or a mild TBI when the level of GFAP is less than about 9.0 pg/mL; treating the subject for a moderate, severe, or moderate to severe TBI when the level of UCH-L1 is greater than about 73.5 pg/mL, or a mild TBI when the level of UCH-L1 is less than about 73.5 pg/mL; or treating the subject based on whether both GFAP and UCH-L1 are above or below those thresholds.
CT triage tied to UCH-L1 and/or GFAP cutoff levels and severity-directed treatment
Performing a head computed tomography (CT) scan on the subject when the level of GFAP is greater than about 9.0 pg/mL, or performing a head CT scan when the level of UCH-L1 is greater than about 73.5 pg/mL, or performing a head CT scan when both the level of GFAP is greater than about 9.0 pg/mL and the level of UCH-L1 is greater than about 73.5 pg/mL, and treating the subject for a moderate, severe, or moderate to severe TBI; and treating the subject for a mild TBI.
Across the independent claims, the core coverage is the use of hyperacute assays for UCH-L1 and/or GFAP from blood, serum, plasma, or CSF samples obtained within about 2 hours, with quantitative biomarker thresholds to classify TBI severity and drive treatment; in one claim, the same biomarker thresholds are also used to trigger a head CT scan.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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