ASSAYS AND METHODS FOR SELECTING A TREATMENT REGIMEN FOR A SUBJECT WITH DEPRESSION

摘要

The present invention provides assays, methods and compositions for selecting a treatment regimen for a patient having depression or at risk for depression and/or treating at least one symptom of depression in the subject, based on the recognition that specific combinations of single nucleotide polymorphisms (SNPs) are associated with a therapeutic response to a folate-comprising compound. Provided herein are also methods for improving the effectiveness of an antidepressant drug administered to a subject with depression or at risk for depression by administering an adjunctive therapy of a folate-comprising compound to the subject if the subject carries a specific combination of SNPs that are predictive of a therapeutic response. Furthermore, provided herein are compositions of the folate-comprising compound.

主权项

1. An assay for selecting a treatment regimen for a human subject diagnosed as having depression or having a risk for depression, the assay comprising:
(a) analyzing a sample from the subject to determine the genotype of at least two genetic biomarkers selected from the group consisting of methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), GTP cyclohydrolase 1 (GCH1), catechol-O-methyltransferase (COMT), and a combination thereof: (b) detecting by genotyping for the presence or absence of a single nucleotide polymorphism (SNP) in each of the at least two genetic biomarkers, wherein the presence of the SNP is set forth as the following:
(i) a SNP at position 677 of SEQ ID NO. 1 or position 27 of SEQ ID NO: 7 as identified as rs1801133 comprising at least one thymine “T” allele for MTFHR;(ii) a SNP at position 2756 of SEQ ID NO: 2 or position 27 of SEQ ID NO: 9 as identified as rs1805087 comprising at least one guanine “G” allele for MTR;(iii) a SNP at position 27 of SEQ ID NO: 18 as identified as rs8007267 comprising at least one thymine “T” allele for GCH1;(iv) a SNP at position 27 of SEQ ID NO: 24 as identified as rs4680 comprising two guanine “G” alleles for COMT; and (c) selecting the treatment regimen comprising an effective amount of a folate-comprising compound based on the presence of said SNPs.