Diagnosis and Prognosis of Multiple Sclerosis

Patent metadata

Field	Value
Publication number	US-2016208332-A1
Application number	US-201615093456-A
Country	US
Kind code	A1
Filing date	Apr 7, 2016
Priority date	Aug 24, 2010
Publication date	Jul 21, 2016
Grant date	—

Abstract

The present invention provides a method for determining whether an individual with relapsing-remitting multiple sclerosis will suffer a relapse or respond to treatment for MS. A ratio of mRNA levels of Response Gene to Complement-32, FasL or IL-21 to L13 determined for an individual provides a normalized level which is compared to a cut-off value. A normalized level of Response Gene to Complement-32 greater than 2.52, a normalized level of FasL greater than 85.4 and a normalized level of IL-21 less than 11.9, respectively, indicates the individual will have or is having a relapse of multiple sclerosis. Also provided are methods for determining whether an individual will respond positively or is responding positively to glatiramer treatment and whether the individual is in a period of stable disease or is not at risk for relapse of multiple sclerosis by comparing normalized levels with the respective cut-off levels.

First claim

What is claimed is:

1 . A method for determining whether an individual with relapsing-remitting multiple sclerosis will suffer a relapse, comprising the step of:
measuring a first mRNA level of Response Gene to Complement-32, FasL or IL-21 in peripheral blood mononuclear cells of said individual; measuring a second mRNA level of L13 in peripheral blood mononuclear cells of said individual; calculating a ratio of the first mRNA level to the second mRNA level to obtain a normalized level of the Response Gene to Complement-32, FasL or IL-21; and comparing said normalized level to a cut-off value for Response Gene to Complement-32, FasL or IL-21 to determine whether said individual will have or is having a relapse of multiple sclerosis.

2 . The method of claim 1 , wherein a normalized level of Response Gene to Complement-32 less than a cut-off value of 1.27 indicates that said individual will have or is having a relapse of multiple sclerosis.

3 . The method of claim 1 , wherein a normalized level of Response Gene to Complement-32 less than a cut-off value of 1.27 from one day to the next indicates that said individual will have or is having a relapse of multiple sclerosis.

4 . The method of claim 1 , wherein a normalized level of Response Gene to Complement-32 less than a cut-off value of 1.27 from one week to the next indicates that said individual will have or is having a relapse of multiple sclerosis.

5 . The method of claim 1 , wherein a normalized level of Response Gene to Complement-32 less than a cut-off value of 1.27 from one month to the next indicates that said individual will have or is having a relapse of multiple sclerosis.

6 . The method of claim 1 , wherein a normalized level of FasL less than a cut-off value of 52.6 indicates that said individual will have or is having a relapse of multiple sclerosis.

7 . The method of claim 1 , wherein a normalized level of FasL less than a cut-off value of 52.6 from one day to the next indicates that said individual will have or is having a relapse of multiple sclerosis.

8 . The method of claim 1 , wherein a normalized level of FasL less than a cut-off value of 52.6 from one week to the next indicates that said individual will have or is having a relapse of multiple sclerosis.

9 . The method of claim 1 , wherein a normalized level of FasL less than a cut-off value of 52.6 from one month to the next indicates that said individual will have or is having a relapse of multiple sclerosis.

10 . The method of claim 1 , wherein a normalized level of IL-21 greater than a cut-off value of 16.9 indicates that said individual will have or is having a relapse of multiple sclerosis.

11 . The method of claim 1 , wherein a normalized level of IL-21 greater than a cut-off value of 16.9 from one day to the next indicates that said individual will have or is having a relapse of multiple sclerosis.

12 . The method of claim 1 , wherein a normalized level of IL-21 greater than a cut-off value of 16.9 from one week to the next indicates that said individual will have or is having a relapse of multiple sclerosis.

13 . The method of claim 1 , wherein a normalized level of IL-21 greater than a cut-off value of 16.9 from one month to the next indicates that said individual will have or is having a relapse of multiple sclerosis.

14 . The method of claim 1 , wherein the peripheral blood mononuclear cells are CD4+ T-cells.

15 . A method for determining whether an individual with relapsing-remitting multiple sclerosis will respond positively to glatiramer treatment for multiple sclerosis, comprising the step of:
administering the glatiramer treatment to said individual; and measuring the mRNA levels of Response Gene to Complement-32, FasL and IL-21 in peripheral blood mononuclear cells of said individual after said treatment; measuring the mRNA level of L13 in peripheral blood mononuclear cells of said individual; calculating said mRNA levels of Response Gene to Complement-32, FasL and IL-21 by the mRNA level of L13 to obtain normalized levels of Response Gene to Complement-32, FasL and IL-21; and comparing said normalized levels of Response Gene to Complement-32, FasL and IL-21 to a cut-off values, wherein normalized levels of at least one of a normalized level of Response Gene to Complement-32 greater than 2.52, a normalized level of FasL greater than 85.4 and a normalized level of IL-21 less than 11.9, respectively in the individual indicates that the individual will respond positively or is responding positively to said treatment.

16 . The method of claim 15 , wherein said mRNA level of said Response Gene, FasL and IL-21 to Complement-32 is measured daily, weekly or monthly.

17 . The method of claim 15 , wherein normalized levels of at least one of Response Gene to Complement-32 greater than 2.52, greater than 85.4 and less than 11.9 in said individual from one measurement to the next indicates that said individual will respond positively or is responding positively to glatiramer treatment.

18 . The method of claim 15 , wherein normalized levels of at least one of Response Gene to Complement-32 greater than 2.52, greater than 85.4 and less than 11.9 from one month to the next in said individual indicates that said individual will respond positively or is responding positively to a pharmacologic treatment for multiple sclerosis.

19 . The method of claim 15 , wherein peripheral blood mononuclear cells are CD4+ T-cells.

20 . A method for determining whether an individual with relapsing-remitting multiple sclerosis is in a period of stable disease or is not at risk for relapse of multiple sclerosis, comprising the step of:
measuring the mRNA level of Response Gene to Complement-32, FasL and IL-21 in peripheral blood mononuclear cells of said individual for at least two times sequentially; measuring the mRNA level of L13 in peripheral blood mononuclear cells of said individual; calculating said mRNA levels of Response Gene to Complement-32 by the mRNA level of L13 to obtain a normalized level of Response Gene to Complement-32; and comparing said normalized level of Response Gene to Complement-32 to a previous measurement of normalized level of Response Gene to Complement-32, wherein a significantly higher normalized level of Response Gene to Complement-32 than a previous measurement thereof in said individual indicates that said individual is in a period of stable disease or is not at risk for relapse of multiple sclerosis.

Assignees

• Rus Horea
• Cudrici Cornelia
• Tegla Cosmin
• Univ Maryland

Inventors

• Rus Horea
• Cudrici Cornelia
• Tegla Cosmin

Classifications

• C12Q1/6883 Primary

  for diseases caused by alterations of genetic material · CPC title

• C12Q2600/118

  Prognosis of disease development · CPC title

• C12Q2600/106

  Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism · CPC title

• C12Q2600/112

  Disease subtyping, staging or classification · CPC title

• C12Q2600/158

  Expression markers · CPC title