Method for Diagnosing Multiple Sclerosis

a multiple sclerosis and multiple sclerosis technology, applied in the field of multiple sclerosis diagnosis, can solve the problems of poor correlation between mri results and disease activity, persistent disability in young adults, and high cost of routine use of mri, and achieve the effect of elevating serum levels

Inactive Publication Date: 2010-04-01
GLYCOMINKS LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0008]The invention is based in part on the discovery that MS patients have elevated serum levels of auto antibodies of IgG, IgA, IgM that bind the glycan structures Glc (α) or Glc (α 1-4) Glc (α) or Glc (α 1-4) Glc (β) as compared to the serum levels of these autoantibodies in healthy individuals. In addition, the same autoantibodies specific for these glycan structures are elevated during the exacerbation state as compared to the level observed in patients in remission and healthy individuals. A high correlation has also been observed between IgM anti-Glc (α)antibody serum levels in females, clinically diagnosed (relapsing-remitting) MS patients, and the women's EDSS (Expanded Disability Status Scale) score. The high correlation indicates that the levels of IgM anti-α-Glucose in serum can act as a clinical surrogate endpoint marker for the activity of the disease and a way to track the efficacy of a drug compound in clinical trials.
[0009]Monitoring the levels of those antibodies in the blood of MS suspected patients facilitates quick and cost effective early diagnosis of MS patients and early prescribing of disease modifying drugs. Monitoring of the levels of those antibodies in the blood of defined MS patients will also enable quick and cost effective monitoring of the effects of prescribed drugs, and early detection of attacks, enabling early prophylactic treatment.
[0010]Among the additional advantages of the invention are that the existence of MS in patients can be determined at an earlier stage of the disease, when its symptoms may resemble many other MS-like diseases. Early diagnosis allows physicians to treat MS earlier in the course of the disease, thereby minimizing or preventing the damage caused by the destruction of myelin and disabilities brought about by this destruction. In addition, the methods disclosed herein enable physicians to follow MS patients regularly in order to assess the disease severity, to monitor therapy, and change treatment once signs for coming attacks appear. For example, an increase in biomarkers indicative of an MS attack may warrant administration to the patient of methylpredisone, which is a general anti inflammatory agent commonly administered during attacks.
[0012]The biomarkers disclosed herein can additionally act as a surrogate end point for assessing the response of a patient to the tested drug in a cost effective way. A surrogate end point based on a serological test facilitates efficient testing of new potential MS drugs.

Problems solved by technology

It is a common cause of persistent disability in young adults.
MRI is a physical method for assessment of brain lesions and is expensive for routine use.
Moreover, the correlation between MRI results and disease activity is poor.
Cerebrospinal Puncture is an un pleasant invasive procedure that is not suitable for routine use.
In addition, both methods assess damage only after it has occurred; neither method can predict the onset of attacks.
A further disadvantage in testing for OCB in CSF and MRI as a way to diagnose MS is that a negative OCB or MRI will not preclude the existence of MS.

Method used

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  • Method for Diagnosing Multiple Sclerosis
  • Method for Diagnosing Multiple Sclerosis
  • Method for Diagnosing Multiple Sclerosis

Examples

Experimental program
Comparison scheme
Effect test

example 1

Comparison Between Antiglycan Antibodies in the Serum of Multiple Sclerosis (MS) Patients and Normal Population

[0078]An anti-glycan antibody (Igs) profile was obtained using GlycoChip® arrays (Glycominds, Ltd., Lod, Israel, Cat No. 9100). The arrays were constructed using procedures described in WO00 / 49412. Anti-glycan antibody profiles of 40 multiple sclerosis patients and 40 sex and aged matched normal blood donors were compared.

[0079]All serum samples were tested using GlycoChip® plates (Glycominds Ltd., Lod, Israel, Cat No. 9100), which was an array of mono and oligosaccharide covalently attached to a reduced volume 384 wells micro titer plate. The mono and oligosaccharides displayed on the array are listed in FIG. 4. A translation of the LinearCode™ syntax used to describe glycan structure to IUPAC nomenclature can be found in Table 1.

[0080]The sera of healthy volunteers and MS patients volunteers who had signed an informed consent form were collected in evacuated silicon coate...

example 2

Differences in the Levels of Anti-Glc (α), and Anti-Glc (α 1-4) Glc (α), a IgM Antibodies in the Serum Between Ms Patients in Attack, Stable Ms Patients and Healthy Population

[0087]A glycan array was used to search for biomarkers among the human serum glycan binding antibody repertoire to differentiate between a healthy population and a group of Multiple Sclerosis (MS) patients, and between MS patients in exacerbation and remission stages. This example demonstrates that two IgM antibodies, anti-Glc (α) and anti-Glc (α 1-4) Glc (α), are found at significantly higher levels in MS patients than in healthy people (sensitivity and specificity of 60% and 93%, respectively), and in MS patients in an exacerbation stage relative to patients in a remission stage (sensitivity and specificity of 89% and 71%, respectively). Also provided is an anti-glycan antibody profile for a healthy population, including a range of variation during a 13 week interval.

[0088]The temporal stability of antiglycan...

example 4

Anti-Glycan Antibody Profile (AGAP) in a Normal Human Population

[0096]Total Ig antibody binding (as detected with Protein A) of 72 individual sera to 34 mono- and oligosaccharides (FIG. 11 and Table 5), and IgG, IgA, and IgM binding of 200 sera to six mono- and oligosaccharides (FIG. 15A-C) was determined. The strongest signals were recorded for antibodies against GlcNAc (α) and L-Rha (α), while lower levels were observed against β4-linked oligosaccharides of glucose, GlcNAc (β), GlcNAC (β 1-4) GlcNAC (β), Gal (α) and Gal (a 1-3) Gal (β 1-4) GlcNAc (β). This is in good agreement with previously published data showing the distribution of anti-glycan antibodies in a commercially available human serum pool (WO02 / 064556). The AGAP of subclasses IgG and IgA were similar to the total Ig AGAP, while that of IgM was lower and more uniform among the different glycans. The anti-glycan antibodies of the population tended to fit a lognormal distribution see FIG. 15A-15C. It is evident that cons...

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Abstract

Disclosed is a method for diagnosing multiple sclerosis and more particularly to a method for diagnosing multiple sclerosis by measuring levels of antibodies to glycans in a biological sample.

Description

RELATED APPLICATIONS[0001]This application claims priority to U.S. Ser. No. 60 / 400,914, filed Aug. 2, 2002; U.S. Ser. No. 60 / 447,076, filed Feb. 13, 2003; U.S. Ser. No. 60 / 462,984 filed Apr. 15, 2003; and U.S. Ser. No. 60 / 473,231, filed May 23, 2003. The contents of these applications are incorporated herein by reference in their entireties.FIELD OF THE INVENTION[0002]The invention relates generally to a method for diagnosing multiple sclerosis and more particularly to a method for diagnosing multiple sclerosis by measuring levels of antibodies to glycans in a biological sample.BACKGROUND OF THE INVENTION[0003]Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system. It is a common cause of persistent disability in young adults. In patients suffering from MS, the immune system destroys the myelin sheet of axons in the brain and the spinal chord, causing a variety of neurological pathologies. In the most common form of MS, Relapsing-Remitting...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12Q1/02G01N33/68C12Q1/68G01N33/53G01N33/564G01N33/567
CPCG01N33/564Y10S436/811G01N2800/285G01N2400/10A61P25/00
Inventor DOTAN, NIRDUKLER, AVINOAMSCHWARZ, MIKAELGARGIR, ARI
Owner GLYCOMINKS LTD
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