Diagnosis and treatment of traumatic brain injury
AssigneeUniversity of South Florida
InventorsSubhra Mohapatra, Shyam S. Mohapatra, Keith Ronald Pennypacker, Mahasweta Das, Christopher Charles Leonardo
Life of this patent
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Abstract
The subject invention identifies CC chemokine ligand 20 (CCL20) as a novel biomarker for diagnosis of traumatic brain injury and/or neurodegeneration in the brain. The subject invention also provides treatment methods for traumatic brain injury and/or neurodegeneration in the brain by modulating systemic and/or brain-specific CCL20-CCR6 signaling. Also provided are uses of CCL20-CCR6 signaling a target for screening for therapeutic agents that are useful for treatment of traumatic brain injury.
Claims22
A method of diagnosing whether a subject has traumatic brain injury, comprising:
- a) determining CC chemokine ligand 20 (CCL20) level in a biological sample obtained of the subject;
- and
- b) comparing the CCL20 level in the biological sample of the subject to a predetermined reference value, and diagnosing the subject as having traumatic brain injury if the CCL20 level in the biological sample of the subject is higher than the predetermined reference value.
A method of diagnosing whether a subject has neurodegeneration in the brain, comprising:
- a) determining CC chemokine ligand 20 (CCL20) level in the biological sample of the subject;
- and
- b) comparing the CCL20 level in a biological sample of the subject to a predetermined reference value, and diagnosing the subject as having neurodegeneration in the brain if the CCL20 level in the biological sample of the subject is higher than the predetermined reference value.
A method for treating a subject who has traumatic brain injury, comprising one or more of the following steps:
- a) modulating or reducing CCL20 level in the subject;
- b) modulating or reducing CCR6 level in the subject;
- c) modulating or inhibiting binding of CCL20 to CCR6 in the subject;
- and
- d) modulating or inhibiting CCL20 signaling in the subject.
A method for screening for therapeutics for treatment of traumatic brain injury, comprising:
- a) administering a candidate molecule to an animal subject having a traumatic brain injury,
- wherein the candidate molecule is selected from an agent that modulates or reduces levels of CCL20, an agent that modulates or reduces levels of CCR6, an agent that modulates or inhibits binding of CCL20 to CCR6, an agent that modulates or inhibits CCR6 signaling, and an agent that modulates or inhibits expression of CCL20 and/or CCR6;
- b) determining a level of neuroinflammation and/or neurodegeneration in brain tissue of the animal subject;
- and
- c) selecting the candidate molecule if said molecule reduces the level of neuroinflammation and/or neurodegeneration in brain tissue of the animal subject, when compared to that of a control animal subject that received the same brain injury but is untreated with said candidate molecule.
A kit for diagnosis of traumatic brain injury and/or for diagnosis of neurodegeneration in the brain, wherein the kit comprises one or more of the following agents:
- (1) an antibody that specifically binds to CCL20 or an antibody fragment thereof;
- and
- (2) an oligonucleotide complementary to a nucleic acid sequence encoding a CCL20 protein, an oligonucleotide complementary to a fragment of a nucleic acid sequence encoding a CCL20 protein.
A therapeutic composition for treatment of traumatic brain injury and/or treatment of neurodegeneration in the brain, wherein the composition comprises one or more of the following therapeutic agents:
- (1) an antibody that specifically binds to CCL20 or an antibody fragment thereof that specifically binds to CCL20, and/or an antibody that binds specifically to CCR6 or an antibody fragment thereof that specifically binds to CCR6;
- and
- (2) an antisense molecule against CCL20, and/or an antisense molecule against CCR6.
Dependencies are inferred from the claim text.