Administration regime

Abstract

A method for determining a folate substance administration regime is disclosed. The method comprises: quantifying, in a sample drawn from a patient, the expression level of at least one of the genes SLC46A1, SLC19A1, FPGS, ABCC3, MTHFD1L, GGH, MTHFD1, MTFMT, and ATIC; and establishing whether the expression level is high or low. A high expression level of at least one of said genes determines that said folate substance administration regime involves the administration of [6R]-methylenetetrahydrofolate and/or a folate substance upstreams of [6R]-methylenetetrahydrofolate in the metabolic pathway. A low expression level of at least one of said genes determines that said folate substance administration regime involves the administration of [6R]-methylenetetrahydrofolate. Also disclosed is a kit for determining such a folate substance administration regime.

1 . A method for determining a treatment regime comprising administration of a folate to a patient in need thereof, said method comprising:
 (a) quantifying, in a sample obtained from said patient, the expression level of at least one gene selected from the group consisting of SLC46A1, SLC19A1, FPGS, ABCC3, SHMT1, MTHFD1L, GGH, MTHFD1, MTFMT, and ATIC; and   (b) establishing whether said expression level is high or low,   wherein a low expression level of at least one of said genes determines that said treatment regime will comprise the administration of [6R]-methylenetetrahydrofolate to a patient in need thereof;   and wherein a high expression level of at least one of said genes determines that said treatment regime will comprise the administration of a folate selected from the group consisting of folic acid, [6R,S]-5-CH 3 -tetrahydrofolate, [6S]5-CH 3 -tetrahydrofolate, [6R,S]-5-CH 2 -tetrahydrofolate, [6S]-5-CHO-tetrahydrofolate, and [6R,S]-5-CHO-tetrahydrofolate to a patient in need thereof.   
     
     
         2 . A method according to  claim 1 , wherein the step of quantifying the expression level of at least one of said genes is performed by real-time quantitative PCR. 
     
     
         3 . A method according to  claim 1 , wherein the expression level of each of said genes is expressed as the Ct value normalized to the mean of the Ct values for an endogenous house-keeping gene selected from the group consisting of β-actin and GAPDH. 
     
     
         4 . A method according to  claim 1 , wherein the step of establishing whether said expression level is high or low comprises comparing the expression level of at least one of said genes with a predetermined cutoff value. 
     
     
         5 . A method according to  claim 4 , wherein:
 the predetermined cutoff value for SLC46A1 is 9.8;   the predetermined cutoff value for SLC19A1 is 7.8;   the predetermined cutoff value for FPGS is 5.5;   the predetermined cutoff value for ABCC3 is 6.6;   the predetermined cutoff value for MTHFD1L is 6.3;   the predetermined cutoff value for GGH is 6.2;   the predetermined cutoff value for MTHFD1 is 6.9;   the predetermined cutoff value for MTFMT is 7.2; and   the predetermined cutoff value for ATIC is 6.0;   wherein each predetermined cutoff value is expressed as a Ct value normalized to a mean Ct value for endogenous house-keeping genes selected from the group consisting of β-actin and GAPDH, and   wherein a high expression level is indicated by an expression level below a predetermined cutoff value, and a low expression level is indicated by an expression level above a predetermined cutoff value.   
     
     
         6 . A method according to  claim 1 , said method comprising quantifying the expression level of at least one of the genes SLC46A1, SLC19A1, and ABCC3; at least one of the genes FPGS, and GGH; or at least one of the genes MTHFD1L, MTHFD1, MTFMT, and ATIC. 
     
     
         7 . A method according to  claim 1 , wherein said sample is obtained from a tumor of said patient. 
     
     
         8 . A method for identifying a patient for a treatment regime, said treatment regime comprising administration of [6R]-methylenetetrahydrofolate to said patient, said method comprising:
 (a) quantifying, in a sample obtained from said patient, an expression level of at least one gene selected from the group consisting of SLC46A1, SLC19A1, FPGS, ABCC3, SHMT1, MTHFD1L, GGH, MTHFD1 , MTFMT, and ATIC; and   (b) establishing whether said expression level is high or low,   wherein a low expression level of at least one of said genes identifies said patient for administration of [6R]-methylenetetrahydrofolate.