This invention is a blood-based immunoassay that uses a tau-binding antibody reagent to selectively detect brain-derived tau protein in patient samples. By measuring tau that originates from the brain rather than from peripheral tissues, it supports the identification of traumatic brain injury (TBI) and the assessment of patient outcomes.
Description
Unmet Need - Current blood-based tau measurements can be confounded by tau from peripheral tissues, whereas this assay binds brain-derived tau and does not bind peripheral (big) tau, giving a more brain-specific TBI readout.
The technology is a method that brings a patient sample, such as blood or plasma, into contact with an antigen-binding reagent (for example, an antibody or antibody fragment) that recognizes brain-derived tau. The reagent targets an epitope in exon 5 of brain-derived tau and does not bind peripheral “big tau.” Because it distinguishes the two forms, the signal reflects tau of brain origin.
Binding is detected with an immunoassay. The presence of brain-derived tau indicates that the patient has suffered a TBI, and the measured amount, compared against a threshold of about 1 to 10 pg/mL, indicates a favorable or unfavorable outcome.
Applications
- Blood-based diagnostic tests for confirming TBI in emergency and trauma settings
- Prognostic tests that stratify TBI patients by expected outcome
- Neurocritical care and intensive care monitoring of patients with severe brain injury
- Clinical trial enrichment and endpoint tools for TBI therapeutics
- Research and reference-lab assay kits for brain-specific tau measurement
Advantages
- Selectively detects brain-derived tau without binding peripheral big tau
- Uses a minimally invasive blood sample, with CNS samples also applicable
- Ultrasensitive detection, with a functional lower limit of quantification of about 0.047 pg/mL
- Supports both TBI detection and outcome prediction
- Works with standard immunoassay formats, in either a 2-step or 3-step protocol
Invention Readiness
The assay has been developed and analytically validated on an ultrasensitive immunoassay platform. Validation covered specificity for brain-derived tau over big tau, repeatability, dilution linearity and spike recovery. In a proof-of-concept cohort of 63 participants (controls, chronic-mixed TBI and acute-severe TBI), brain-derived tau levels were significantly higher in acute-severe TBI than in controls and chronic-mixed TBI. Levels were also higher in patients with unfavorable functional outcomes. Cross-validated discrimination of severe-acute TBI from controls was stron.
IP Status
Patent Pending
