Methods of diagnosis and treatment
AssigneeOncomethylome Sciences SA
InventorManel Esteller
Life of this patent
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Abstract
A method of diagnosing a disease in which an miRNA is expressed at a lower level comprises, in a test sample obtained from a subject, determining the methylation status of at least one gene encoding the miRNA in the sample, wherein the presence of methylation is indicative of the presence of the disease. Methylation of the gene causes a down regulation in expression which may also be monitored. Related methods and kits are also described based upon methylation of miRNA encoding genes. The primary miRNA of interest is 124a miRNA.
Claims61
A method of diagnosing a disease in which an miRNA is expressed at a lower level comprising, in a test sample obtained from a subject, determining the methylation status of at least one gene encoding the miRNA in the sample, wherein the presence of methylation is indicative of the presence of the disease.
A method for predicting the likelihood of successful treatment or resistance to treatment of a disease in which an miRNA is expressed at a lower level with a DNA demethylating agent and/or a DNA methyltransferase inhibitor and/or a HDAC inhibitor comprising determining the methylation status of at least one gene encoding the miRNA in a sample obtained from a subject, wherein if the gene is methylated the likelihood of successful treatment is higher than if the gene is unmethylated and wherein if the gene is unmethylated the likelihood of resistance to treatment is higher than if the gene is methylated.
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A method of selecting a suitable treatment regimen for a disease in which an miRNA is expressed at a lower level comprising determining the methylation status of at least one gene encoding the miRNA in a sample obtained from a subject, wherein if the gene is methylated a DNA demethylating agent and/or a DNA methyltransferase inhibitor and/or a HDAC inhibitor is selected for treatment.
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A method of diagnosing cancer comprising, in a test sample obtained from a subject, determining the expression levels or activity of 124a miRNA in the sample, wherein a reduced level of expression or activity is indicative of the presence of the disease.
A method for predicting the likelihood of successful treatment or resistance to treatment of cancer with a DNA demethylating agent and/or a DNA methyltransferase inhibitor and/or a HDAC inhibitor comprising determining the expression levels or activity of 124a miRNA in a test sample obtained from a subject, wherein a reduced level of expression or activity is indicative of the likelihood of successful treatment being higher than if the expression levels or activity are higher and wherein an increased level of expression or activity is indicative of the likelihood of successful treatment being lower than if the expression levels or activity are lower.
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A method of selecting a suitable treatment regimen for cancer comprising determining the expression levels or activity of 124a miRNA in a test sample obtained from a subject, wherein if the expression levels or activity are lower a DNA demethylating agent and/or a DNA methyltransferase inhibitor and/or a HDAC inhibitor is selected for treatment.
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A recombinant construct capable of expressing an miRNA comprising the nucleotide sequence set forth as SEQ ID NO:
- 1 or a functional derivative thereof with the ability to down-regulate CDK6 protein expression.
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A method of treating a condition characterised by methylation of miRNA comprising administering to a patient in need of treatment a demethylating agent in an amount effective to restore miRNA function.
A method of treating a condition characterised by methylation of miRNA comprising administering to a patient in need of treatment one or more miRNAs, wherein the administered miRNAs complement miRNA function suppressed by methylation in the patient.
A method of treating cancer in a patient comprising reducing CDK6 levels and/or activity.
A pharmaceutical composition comprising an miRNA together with a suitable carrier/excipient/diluent.
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A kit for:
- (a) diagnosing a disease in which an miRNA is expressed at a lower level;
- and/or
- (b) predicting the likelihood of successful treatment of a disease in which an miRNA is expressed at a lower level and/or the likelihood of resistance to treatment of a disease in which an miRNA is expressed at a lower level with a DNA demethylating agent and/or a DNA methyltransferase inhibitor and/or a HDAC inhibitor, and/or
- (c) selecting a suitable treatment regimen for a disease in which an miRNA is expressed at a lower level
- comprising carrier means containing therein a set of primers for use in detecting the methylation status of at least one gene encoding the miRNA or for use in detecting the expression level of an miRNA which is expressed at a lower level in the disease.
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Dependencies are inferred from the claim text.