Methods of predicting methotrexate efficacy and toxicity

C - Chemistry – Metallurgy – 12 – Q

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C12Q 1/68 (2006.01)

Patent

CA 2606424

The present invention provides methods for analyzing genetic and/or metabolite biomarkers to individualize methotrexate (MTX) therapy. For example, the assay methods of the present invention are useful for predicting whether a patient will respond to MTX and/or has a risk of developing toxicity to MTX based upon the genotype of one or more folate pathway genes. The assay methods of the present invention are also useful for optimizing the dose of MTX in a patient already receiving the drug to achieve therapeutic efficacy and/or reduce toxic side-effects based upon the genotype of one or more folate pathway genes. In addition, the assay methods of the present invention are useful for predicting or optimizing the therapeutic response to MTX in a patient based upon the methotrexate polyglutamate and/or folate polyglutamate levels in a sample from the patient.

La présente invention concerne des procédés qui permettent d'analyser des biomarqueurs génétiques et/ou métabolitiques afin d'individualiser une thérapie par le méthotrexate (MTX). Les procédés de l'invention permettent, par exemple, de prédire, sur la base du génotype d'un ou plusieurs gènes de la voie du folate, si un patient répondra au MTX et/ou s'il présente un risque de développer une toxicité au MTX. Les procédés d'analyse précités sont également utilisés pour optimiser, sur la base du génotype d'un ou plusieurs gènes de la voie du folate, la dose de MTX chez un patient qui reçoit déjà le médicament afin d'arriver à une efficacité thérapeutique et/ou de réduire les effets secondaires toxiques. En outre, les procédés de l'invention permettent de prédire ou d'optimiser la réponse thérapeutique au MTX chez un patient, sur la base des niveaux de méthotrexate polyglutamate et/ou de folate polyglutamate dans un prélèvement provenant du patient.

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