Methods of diagnosing a disease and methods of monitoring treatment of a disease by quantifying a non-reducing end glycan residual compound and comparing to a second biomarker

Patent metadata

Field	Value
Publication number	US-9340822-B2
Application number	US-201414462285-A
Country	US
Kind code	B2
Filing date	Aug 18, 2014
Priority date	Jan 2, 2009
Publication date	May 17, 2016
Grant date	May 17, 2016

Abstract

Provided herein are methods of diagnosing or monitoring the treatment of abnormal glycan accumulation or a disorder associated with abnormal glycan accumulation.

First claim

What is claimed is:

1. A method of determining in an individual the presence, identity, and/or severity of a disease or condition associated with abnormal glycan biosynthesis, degradation, or accumulation, the method comprising:
(a) generating a first biomarker comprising a glycan residual compound, wherein the first 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, wherein prior to enzyme treatment, the first biomarker is not present in abundance in samples from individuals with the disease or condition relative to individuals without the disease or condition, and wherein the first biomarker is a non-reducing end biomarker;
(b) generating a second biomarker comprising a glycan residual compound, wherein the second 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 in the same or different digestion step as provided in step (a), wherein prior to enzyme treatment, the second biomarker is not present in abundance in samples from individuals with the disease or condition relative to individuals without the disease or condition, and wherein:
1) the second biomarker is a non-reducing end biomarker different from the first biomarker,
2) the second biomarker is a reducing end biomarker,
3) the second biomarker is an internal glycan biomarker, or
4) when the disease or condition is caused by an abnormal function of a glycan degradation enzyme in the individual, the second biomarker is a biomarker generated by treating the first biomarker with the glycan degradation enzyme that is functioning abnormally in the individual;

(c) using an analytical instrument to detect the presence of and/or measure the amount of the first and second biomarker produced and displaying or recording the presence of or a measure of a population of the first and second biomarkers; and
(d) monitoring and/or comparing the amounts of the first and second biomarkers in a biological sample;
wherein the presence of and/or measure of the amounts of the first and second biomarkers are utilized to determine the presence, identity, and/or severity of the disease or condition; and
wherein the disease or condition is a lysosomal storage disease, cancer, an inflammatory disease, liver disease, bone diseases, an infectious disease, a central nervous system disease, or a cardiovascular disease.

2. The method of claim 1 , wherein the disease or condition is caused by an abnormally functioning glycan degradation enzyme and wherein the abnormally functioning glycan degradation enzyme and the digesting glycan enzyme are of the same type.

3. The method of claim 1 , wherein the non-reducing end biomarker is a monosaccharide.

4. The method of claim 1 , wherein the non-reducing end biomarker is not a monosaccharide.

5. The method of claim 1 , wherein the second biomarker is derived or generated from the reducing end of the same glycan from which the first biomarker was generated.

6. The method of claim 1 , wherein the second biomarker is derived or generated from the internal oligosaccharide structures of the same glycan from which the first biomarker was generated.

7. The method of claim 1 , wherein the disease or condition is caused by an abnormal function of a glycan degradation enzyme in the individual, and wherein the second biomarker can be generated by treating the first biomarker with the glycan degradation enzyme that is functioning abnormally in the individual.

8. The method of claim 1 , wherein the lysosomal storage disease is Mucopolysaccharidosis selected from a group consisting of MPS I, II, IIIA, IIIB, IIIC, IIID, IVA, IVB, VI, and VII.

9. The method of claim 1 , wherein the disease or condition associated with abnormal glycan biosynthesis, degradation, or accumulation is Metachromatic Leukodystrophy, Krabbe disease, Tay Sachs, Sandhoff, AB Variant, or GM-1 Gangliosidosis.

10. The method of claim 1 , wherein the at least one digesting glycan enzyme is a lyase.

11. The method of claim 8 , wherein the disease or condition is:
(i) MPS I and the at least one digesting glycan enzymes is iduronidase;
(ii) MPS II and the at least one digesting glycan enzyme is 2-sulfatase;
(iii) MPS IIIA and the at least one digesting glycan enzyme is N-sulfatase;
(iv) MPS IIIB and the at least one digesting glycan enzyme is hexosaminidase or deacetylase;
(v) MPS IIIC and the at least one digesting glycan enzyme is hexosaminidase or N-acetyl-transferase;
(vi) MPS IIID and the at least one digesting glycan enzyme is 6-O-sulfatase;
(vii) MPS IVA and the at least one digesting glycan enzyme is 6-O-sulfatase, galactosidase, N-acetyl-galactosidase, or hexosaminidase;
(viii) MPS IVB and the at least one digesting glycan enzyme is galactosidase;
(ix) MPS VI and the at least one digesting glycan enzyme is 4-O-sulfatase; or
(x) MPS VII and the at least one digesting glycan enzyme is β-glucuronidase.

12. The method of claim 9 , wherein the at least one digesting glycan enzyme is selected from a group consisting of 3-O-sulfatase, galactosidase, hexosaminidase and β-galactosidase.

13. The method of claim 1 , wherein disease or condition is:
(i) an infectious disease, the infectious disease being a bacterial or fungal infection, and the at least one digesting enzyme is a mannosidase, fucosidase, glucosidase, galactosidase, hexosaminidase, arabinosidase, xylosidase, ribosidase, lyxosidase, talosidase, idosidase, gulosidase, altrosidase, or allosidase;
(ii) an infectious disease, the infectious disease being a viral infection, and the at least one digesting enzyme is sialidase, α-sialidase, hexosaminidase, galactosidase, fucosidase, or sulfatase;
(iii) a coronary artery disease and the at least one digesting enzymes is sialidase, α-sialidase, hexosaminidase, galactosidase, fucosidase, or sulfatase;
(iv) an inflammatory disease selected from a group consisting of rheumatoid arthritis, psoriatic arthritis, asthma, chronic obstructive pulmonary disorder, lupus, hepatitis, renal disease, sickle cell disease, fibromyalgia, irritable bowel syndrome, and an ulcer, and the at least one digesting enzymes is a sialidase, α-sialidase, hexosaminidase, galactosidase, fucosidase, or sulfatase; or
(v) Alzheimer's disease or Parkinson's disease, and the at least one digesting glycan enzyme is sialidase, hexosaminidase, galactosidase, fucosidase, or sulfatase.

14. The method of claim 1 , wherein the disease or condition associated with abnormal glycan accumulation is selected from a group consisting of alpha mannodidosis, aspartylglucoaminuria, Fabry's disease, fucosidosis, galatosialidosis, Gaucher disease, GM1 gangliosidosis, GM2 activator deficiency, sialidosis, Krabbe disease, metachromatic leukodystrophy, mucolipidosis II, mucolipidosis III, mucolipidosis IV, multiple sulfatase deficiency, Pompe disease, Sandhoff disease, Tay-Sachs disease, AB variant, Schindler disease, alpha mannosidosis, beta mannosidosis, and globoid cell leukodystrophy.

15. The method of claim 14 , wherein the disease or condition is:
(i) alpha mannodidosis, and the at least one digesting glycan enzyme is mannosidase;
(ii) aspartylglucoaminuria, and the at least one digesting glycan enzyme is hexosaminidase;
(iii) Fabry's disease, and the at least one digesting glycan enzyme is galactosidase;
(iv) fucosidosis, and the at least one digesting glycan enzyme is fucosidase;
(v) galatosialidosis, and the at least one digesting glycan enzyme is galactosidase and/or sialidase;
(vi) Gauche

Assignees

• Biomarin Pharm Inc

Inventors

• Crawford Brett E
• Brown Jillian R
• Glass Charles A
• Beitel Jim R
• Jackman Robin M

Classifications

• G01N33/6893

  related to diseases not provided for elsewhere · CPC title

• C12Q1/40

  involving amylase · CPC title

• G01N2800/28

  Neurological disorders · CPC title

• G01N2800/04

  Endocrine or metabolic disorders · CPC title

• C12Q1/42

  involving phosphatase · CPC title