Quantification of non-reducing end glycan residual compounds for determining the presence, identity, or severity of a disease or condition
Provided herein are methods of diagnosing or monitoring the treatment of abnormal glycan accumulation or a disorder associated with abnormal glycan accumulation.
1. A method of determining the presence, identity, and/or severity of a disease or condition in an individual, wherein the disease or condition is associated with abnormal glycan biosynthesis, degradation, or accumulation, the method comprising:
(a) generating a biomarker comprising of one or more non-reducing end glycan residual compound(s), wherein the biomarker is generated by treating a population of glycans, in or isolated from a biological sample from the individual, with at least one digesting glycan enzyme(s), wherein prior to enzyme treatment, the biomarker is not present in abundance in samples from individuals with the disease or condition relative to individuals without the disease or condition;
(b) detecting the presence of and/or measuring the amount of the biomarker produced using an analytical instrument and displaying or recording the presence of or the measure of the biomarker produced; and
(c) correlating the presence of and/or the measure of the amount of the biomarker with the presence, identity, and/or severity of the disease or condition for determining the presence, identity, and/or severity of the disease or condition in the individual,
wherein the disease or condition is mucopolysaccharidosis I (MPS I); and
wherein at least one digesting glycan enzyme is iduronidase.
2. The method of claim 1 , wherein at least one of the non-reducing end glycan residual compound is a monosaccharide.
3. The method of claim 2 , further comprising purifying the biological sample in step (a) prior to enzyme treatment.
4. The method of claim 3 , wherein the process of purifying the biological sample comprises, removing monosaccharides therefrom, removing sulfates therefrom, removing phosphates therefrom, removing acetate therefrom, or a combination thereof.
5. The method of claim 2 , wherein prior to measuring the amount of a population of non-reducing end glycan residual compounds, the non-reducing end glycan residual compounds are labeled with a detectable label and wherein the amount of the generated non-reducing end glycan residual compounds is measured using UV-Vis spectroscopy, IR spectroscopy, mass spectrometry, or a combination thereof.
6. The method of claim 5 , wherein the detectable label is a mass label, a radioisotope label, a fluorescent label, a chromophore label, or affinity label.
7. A method of monitoring the treatment of a disease or condition associated with the abnormal degradation, biosynthesis and/or accumulation of glycans, the method comprising:
(a) following administration of an agent for the treatment of the disease or condition to an individual in need thereof, using an analytical instrument to measure the amount of a population of a biomarker, wherein the biomarker was generated by treating a population of glycans, in or isolated from a biological sample from the individual to provide a transformed biological sample, with at least one digesting glycan enzyme(s), wherein the biomarker comprises one or more non-reducing end glycan residual compounds present in the transformed biological sample, and wherein prior to enzyme treatment, the biomarker is not present in abundance in the biological samples from individuals with the disease or condition relative to individuals without the disease or condition, and
(b) determining whether or not the amount of the biomarker has decreased or has increased compared to the amount of the biomarker prior to administration of the agent, or whether or not the amount of the biomarker has increased at a slower rate compared to the rate of increase prior to administration of the agent; and
wherein the disease or condition is MPS I; and
wherein at least one digesting glycan enzyme is iduronidase.
8. The method of claim 7 , wherein at least one of the non-reducing end glycan residual compound is a monosaccharide.
9. The method of claim 7 , further comprising purifying the biological sample in step (a) prior to enzyme treatment.
10. The method of claim 9 , wherein the process of purifying the biological sample comprises, removing monosaccharides therefrom, removing sulfates therefrom, removing phosphates therefrom, removing acetate therefrom, or a combination thereof.
11. The method of claim 7 , wherein prior to measuring the amount of a population of non-reducing end glycan residual compounds, the non-reducing end glycan residual compounds are labeled with a detectable label and wherein the amount of the generated non-reducing end glycan residual compounds is measured using UV-Vis spectroscopy, IR spectroscopy, mass spectrometry, or a combination thereof.
12. The method of claim 11 , wherein the detectable label is a mass label, a radioisotope label, a fluorescent label, a chromophore label, or affinity label.