Methods for the prognosis and treatment of temporal lobe epilepsy
AssigneeArizona Board of Regents on Behalf of the University of Arizona
InventorMartin Weinand
Life of this patent
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Abstract
Differential expression of specific leukocyte genes involved in canonical pathways of neuroinflammation, oxidative stress, and lipid peroxidation, GABA (γ-aminobutyric acid) inhibition, and AMPA and NMDA receptor signaling is able to predict the severity of temporal lobe epilepsy (TLE). For example, high seizure frequency-TLE is distinguished prognostically from low seizure frequency-TLE by differentially increased specific leukocyte gene expression involved in GABA inhibition and NMDA receptor signaling. Thus, high and low seizure frequency patients represent two mechanistically different forms of temporal lobe epilepsy based on leukocyte gene expression and potentially require distinct treatments.
Claims20
A method of predicting the severity of human temporal lobe epilepsy (TLE) in a subject in need thereof, the method comprising:
- a) obtaining a biological sample from the subject;
- and
- b) measuring the expression levels of one or more leukocyte genes in the biological sample from the subject;
- wherein the subject is predicted to have severe TLE if the levels of the one or more leukocyte genes are down-regulated, or the subject is predicted to have mild TLE if the levels of the one or more leukocyte genes are upregulated.
A method of predicting the severity of human temporal lobe epilepsy (TLE) in a subject in need thereof, the method comprising:
- a) obtaining a biological sample from the subject;
- and
- b) measuring the expression levels of ten or more leukocyte genes in the biological sample from the subject;
- wherein the subject is predicted to have severe TLE if (i) the expression levels of the leukocyte genes selected from a group consisting of Thymidylate Synthase (TYMS), Adenylate Kinase 1 (AK1), Coagulation Factor II Thrombin Receptor (F2R), and G Protein Subunit Beta 5 (GNB5) are upregulated and/or (ii) the expression level of the leukocyte genes selected from a group consisting of Neutrophil Cytosolic Factor 2 (NCF2), Heme Oxygenase (HMOX), Ras Homolog Family Member B (RHOB), Fc Gamma Receptor IIa (FCGR2A), Protein Kinase C Delta (PRKCD), Rac Family Small GTPase 2 (RAC2), Toll Like Receptor 1 (TLR1), Calcineurin Like EF-Hand Protein 1 (CHP1), Tumor Necrosis Factor Receptor Superfamily Member 1A (TNFRSF1A), Interferon Gamma Receptor 1 (IFNGR1), LYN, Myeloid Differentiation Primary Response 88 (MYD88), and Caspase-1 (CASP1) are down-regulated;
- and
- wherein the subject is predicted to have mild TLE if (i) the expression level of the leukocyte genes selected from a group consisting of NCF2, HMOX1, FCGR2A, PRKCD, CHP1, IFNGR1, RHOB, RAC2, TLR1, TNFRSF1A, LYN, MYD88, and CASP are upregulated and/or (ii) the expression levels of the leukocyte genes selected from a group consisting of TYMS, AK1, F2R, and GNB5 are downregulated.
A method of treating a subject with temporal lobe epilepsy (TLE), the method comprising:
- a) determining the severity of the TLE in a subject in need thereof by;
- i. obtaining a biological sample from the subject;
- and
- ii. measuring the expression levels of ten or more leukocyte genes in the biological sample from the subject;
- wherein the subject is predicted to have severe TLE if (i) the expression levels of the leukocyte genes selected from a group consisting of Thymidylate Synthase (TYMS), Adenylate Kinase 1 (AK1), Coagulation Factor II Thrombin Receptor (F2R), and G Protein Subunit Beta 5 (GNB5) are upregulated and/or (ii) the expression level of the leukocyte genes selected from a group consisting of Neutrophil Cytosolic Factor 2 (NCF2), Heme Oxygenase (HMOX), Ras Homolog Family Member B (RHOB), Fc Gamma Receptor IIa (FCGR2A), Protein Kinase C Delta (PRKCD), Rac Family Small GTPase 2 (RAC2), Toll Like Receptor 1 (TLR1), Calcineurin Like EF-Hand Protein 1 (CHP1), Tumor Necrosis Factor Receptor Superfamily Member 1A (TNFRSF1A), Interferon Gamma Receptor 1 (IFNGR1), LYN, Myeloid Differentiation Primary Response 88 (MYD88), and Caspase-1 (CASP1) are down-regulated;
- and
- wherein the subject is predicted to have mild TLE if (i) the expression level of the leukocyte genes selected from a group consisting of NCF2, HMOX1, FCGR2A, PRKCD, CHP1, IFNGR1, RHOB, RAC2, TLR1, TNFRSF1A, LYN, MYD88, and CASP are upregulated and/or (ii) the expression levels of the leukocyte genes selected from a group consisting of TYMS, AK1, F2R, and GNB5 are downregulated;
- and
- b) administering a treatment to the subject based on whether the subject has severe TLE or mild TLE.
Dependencies are inferred from the claim text.