Method for treatment of traumatic brain injury targeting aggregated peptides
Inventors
Lannfelt, Lars • Basun, Hans • WAARA, Erik Rollman
Assignees
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Publication Number
US-11327080-B2
Publication Date
2022-05-10
Expiration Date
Abstract
A method of preventing, alleviating or treating traumatic brain injury in an individual comprises administering to the individual a therapeutically effective and physiologically acceptable amount of an agent capable of reducing the amount of one or more aggregated forms of one or more peptides in the brain. An agent capable of reducing the amount of one or more aggregated forms of one or more peptides in the brain is suitable for use in preventing, alleviating or treating traumatic brain injury. A method for predication of the risk of an individual for complications after a traumatic brain injury comprises detecting one or more aggregated forms of one or more peptides prone to aggregate as a result of a traumatic brain injury event, in the brain of the individual, wherein an increased level of such aggregates in the brain indicates an increased risk for complications.
Core Innovation
The disclosure describes a therapeutic and diagnostic framework for traumatic brain injury (TBI) that targets aggregated peptide species in the brain. The aggregated targets are described as Aβ protofibrils/oligomers, and the disclosure also references α-synuclein and tau as aggregated peptide species.
A method is described for alleviating or treating traumatic brain injury by administering a therapeutically effective and physiologically acceptable amount of an antibody that binds Aβ protofibrils. The antibody is specified as mAb158 or a humanized version thereof.
For diagnosis and prediction, the disclosure describes detecting and measuring aggregated peptide binding in the brain using a labeled antibody that binds Aβ protofibrils. The disclosure further connects peptide aggregate detection with outcomes and reports ApoE genotyping results (ApoE3/E3, ApoE3/E4, ApoE4/E4, ApoE2/E4) associated with levels of Aβ protofibrils shortly after TBI, and includes imaging references such as PET/MRI.
Claims Coverage
The document includes two independent claims. Claim coverage centers on administering mAb158 or a humanized version to alleviate or treat TBI by binding Aβ protofibrils, and on labeling an mAb158 or humanized antibody and measuring localization and amount of aggregated Aβ peptide binding in the brain with traumatic brain injury.
Antibody administration for alleviating or treating TBI via binding Aβ protofibrils
A method of alleviating or treating traumatic brain injury in an individual by administering a therapeutically effective and physiologically acceptable amount of an antibody that binds Aβ protofibrils, wherein the antibody is mAb158 or a humanized version thereof.
Labeled antibody detection and measurement of aggregated Aβ protofibrils binding in the brain
A method of binding an amount of Aβ protofibrils in the brain of an individual having a traumatic brain injury by administering a physiologically acceptable amount of an antibody that binds Aβ protofibrils, wherein the antibody is mAb158 or a humanized version thereof, wherein the antibody is labelled with a detectable label, and measuring the localization and amount of the aggregated Aβ peptide binding with the labelled antibody.
Overall, the claims cover therapy and diagnostic measurement using mAb158 or a humanized version targeting Aβ protofibrils in individuals with traumatic brain injury, including detection via a labeled antibody and measurement of localization and binding amount.
Stated Advantages
Alleviating or treating traumatic brain injury by administering an antibody that binds Aβ protofibrils.
Preventing or alleviating/treating TBI and improving outcomes is described, including avoiding prolonged unconsciousness.
Predictive diagnosis by detecting peptide aggregates in the brain using labeled antibody approaches, including imaging such as PET/MRI.
Documented Applications
Therapeutic administration of mAb158 or a humanized version to alleviate or treat traumatic brain injury in an individual.
Diagnostic/predictive detection by administering a labeled mAb158 or a humanized version antibody and measuring localization and amount of aggregated Aβ peptide binding to aggregated Aβ protofibrils in the brain of an individual with traumatic brain injury.
Use in sub-populations based on traumatic brain injury categories and etiology refinements, including mild, moderate, stroke, or hypoxia-related.
Use with ApoE genotyping refinements, including ApoE4 allele carrier, ApoE3/E4, or ApoE4/E4.
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