Method for assessment of folate phenotypes, disease risk and response to therapy
AssigneeThe Trustees of the University of Pennsylvania
InventorsAlexander Steven Whitehead, Ian A. Blair
Life of this patent
Estimating the term…
Abstract
The invention provides a method for measuring the levels of 5-methyltetrahydrofolate (5-MTHF), tetrahydrofolate (THF), and 5,10-MTHF in a biological sample. The method includes employing an isotope dilution liquid chromatography-multiple reaction monitoring/mass spectrometry (LC-MRM/MS) methodology.
Claims16
A method of measuring the level of folate in a biological sample derived from a subject comprising measuring the level of any combination of various forms of folate selected from the group consisting of 5-methyltetrahydrofolate (5-MTHF), tetrahydrofolate (THF), and 5,10-MTHF or measuring the level of at least one of THF and 5,10-MTHF in said biological sample, wherein said measured level of any combination of various forms of folate selected from the group consisting of 5-MTHF, THF, and 5,10-MTHF or at least one of THF and 5,10-MTHF, is a measurement of said folate level in said biological sample.
A method of identifying a subject that is at risk of having a disease or condition associated with folate/homocysteine metabolism, said method comprising measuring the level of folate in a biological sample derived from said subject comprising measuring the level of any combination of various forms of folate selected from the group consisting of 5-MTHF, THF, and 5,10-MTHF or the level of at least one of THF and 5,10-MTHF in said biological sample, wherein said measured level of any combination of various forms of folate selected from the group consisting of 5-MTHF, THF, and 5,10-MTHF or the level of at least one of THF and 5,10-MTHF, is a measurement of said folate level in said biological sample, wherein a low level of folate in said biological sample compared to the folate level in a biological sample from an otherwise identical healthy subject identifies a subject at risk of having said disease or condition.
A method of evaluating the effect of an agent on a subject having a disease associated with folate/homocysteine metabolism, said method comprising comparing the level of any combination of various forms of folate selected from the group consisting of 5-MTHF, THF, and 5,10-MTHF or the levels of at least one of THF and 5,10-MTHF in a biological sample of a subject following administration of said agent to said subject, to the level of any combination of various forms of folate selected from the group consisting of 5-MTHF, THF, and 5,10-MTHF or the levels of at least one of THF and 5,10-MTHF in an otherwise identical biological sample of a subject not administered said agent, wherein an increased level of any combination of various forms of folate selected from the group consisting of 5-MTHF, THF, and 5,10-MTHF or an increased level of at least one of THF and 5,10-MTHF detected in said biological sample of said subject administered said agent compared to the level of any combination of various forms of folate selected from the group consisting of 5-MTHF, THF, and 5,10-MTHF or the level of at least one of THF and 5,10-MTHF in said otherwise identical biological sample is an indication that said agent increases folate levels in said subject, further wherein a decrease level of any combination of various forms of folate selected from the group consisting of 5-MTHF, THF, and 5,10-MTHF or a decrease level of at least one of THF and 5,10-MTHF detected in said biological sample of said subject administered with said agent compared to the level of any combination of various forms of folate selected from the group consisting of 5-MTHF, THF, and 5,10-MTHF or the level of at least one of THF and 5,10-MTHF in said otherwise identical biological sample of said subject not administered with said agent is an indication that said agent is able to decrease folate levels in said subject.
A method of diagnosing a disease or condition associated with folate/homocysteine metabolism in a subject, said method comprising measuring the level of folate in a biological sample derived from a subject comprising measuring the level of any combination of various forms of folate selected from the group consisting of 5-MTHF, THF, and 5,10-MTHF or the level of at least one of THF and 5,10-MTHF in said biological sample, wherein said measured level of any combination of various forms of folate selected from the group consisting of 5-MTHF, THF, and 5,10-MTHF or the level of at least one of THF and 5,10-MTHF, is a measurement of said folate in said biological sample, wherein a low level of folate in said biological sample compared to the level of folate in a biological sample from an otherwise identical healthy subject identifies a subject at risk of having said disease or condition.
A method of monitoring the progression of a disease or condition associated with folate/homocysteine metabolism in a subject, said method comprising measuring the level of folate in a biological sample derived from said subject comprising measuring the level of any combination of various forms of folate selected from the group consisting of 5-MTHF, THF, and 5,10-MTHF or the level of at least one of THF and 5,10-MTHF in said biological sample, wherein said measured level of any combination of various forms of folate selected from the group consisting of 5-MTHF, THF, and 5,10-MTHF or the level of at least one of THF and 5,10-MTHF, is a measurement of said folate in said biological sample, wherein a low level of folate in said biological sample compared to the level of folate in a biological sample from said subject at an earlier time identifies progression of said disease or condition.
A method of monitoring the progression of a side effect in a subject, said method comprising measuring the level of folate in a biological sample derived from said subject comprising measuring the level of any combination of various forms of folate selected from the group consisting of 5-MTHF, THF, and 5,10-MTHF or the level of at least one of THF and 5,10-MTHF in said biological sample, wherein said measured level of any combination of various forms of folate selected from the group consisting of 5-MTHF, THE, and 5,10-MTHF or the level of at least one of THF and 5,10-MTHF, is a measurement of said folate in said biological sample, wherein a low level of folate in said biological sample compared to the folate level in a biological sample from said subject at an earlier time identifies progression of said side effect.
Dependencies are inferred from the claim text.