Diagnosis method of multiple sclerosis

Patent metadata

Field	Value
Publication number	US-12253530-B2
Application number	US-201917057269-A
Country	US
Kind code	B2
Filing date	May 22, 2019
Priority date	May 22, 2018
Publication date	Mar 18, 2025
Grant date	Mar 18, 2025

Abstract

A method for diagnosing or prognosing, multiple sclerosis including the steps of (a) measuring the amount of at least one first protein as set forth in SEQ ID NO: 1, the at least first protein belonging to the group of proteins: a first protein, a second protein, a third protein, a fourth protein and a fifth protein, as set forth in SEQ ID NO 1 to 5, (b) comparing the amount of the at least first protein with the amount of the same protein in a control sample, and (c) determining the status of the biological sample.

First claim

The invention claimed is:

1. A method for diagnosing multiple sclerosis in an individual suspected to be afflicted by multiple sclerosis, comprising the steps of:
a) measuring, in a biological sample of said individual, the amount of at least one first protein, said at least one first protein comprising the amino acid sequence as set forth in SEQ ID NO: 1, said at least one first protein belonging to the group of proteins consisting of a first protein, a second protein, a third protein, a fourth protein and a fifth protein,
said first protein comprising the amino acid sequence as set forth in SEQ ID NO: 1,
said second protein comprising the amino acid sequence as set forth in SEQ ID NO: 2,
said third protein comprising the amino acid sequence as set forth in SEQ ID NO: 3,
said fourth protein comprising the amino acid sequence as set forth in SEQ ID NO: 4, and
said fifth protein comprising the amino acid sequence as set forth in SEQ ID NO: 5,
b) comparing the amount of said at least one first protein with the amount of the same protein in a control sample of the same nature originating from a healthy individual not afflicted by multiple sclerosis, to establish a protein expression level ratio of said at least one first protein,
c) diagnosing said individual as having multiple sclerosis for the ratio established in step b) for said at least one first protein is higher than, or equal to, 2.

2. The method according to claim 1 , wherein
step a) consists of measuring the amount of at least said first protein, said second protein and said third protein,
step b) consists of comparing the amount of said at least three proteins with the amount of the same proteins in a control sample of the same nature originating from a healthy individual not afflicted by multiple sclerosis, to establish the respective protein expression level ratio for each of said at least three proteins, and
step c) consists of diagnosing said individual as having multiple sclerosis for the ratio established in step b)
for said at least first protein is higher than, or equal to, 2,
for said at least second protein is higher than, or equal to, 2.5, and
for said at least third protein is higher than, or equal to, 1.5.

3. The method according to claim 2 , wherein said individual is diagnosed as having relapsing-remitting multiple sclerosis in step c) for the ratio established in step b)
for said at least first protein is higher than, or equal to, 2,
for said at least second protein is higher than, or equal to, 2.5, and
for said at least third protein is higher than, or equal to 3.

4. The method according to claim 2 , wherein said individual is diagnosed as having multiple sclerosis in step c) for the ratio established in step b)
for said at least first protein is higher than, or equal to, 2,
for said at least second protein is higher than, or equal to 5,
for said at least third protein is higher than, or equal to, 1.5.

5. The method according to claim 1 , wherein said biological sample is a cerebrospinal fluid sample.

6. A method for diagnosing in vitro a central nervous system disease in an individual suspected to be afflicted by such a disease, said method comprising:
a) measuring the amount of at least one first protein, one second protein and one third protein,
said first protein comprising the amino acid sequence as set forth in SEQ ID NO: 1,
said second protein comprising the amino acid sequence as set forth in SEQ ID NO: 2,
said third protein comprising the amino acid sequence as set forth in SEQ ID NO: 3,
said at least one first protein, one second protein and one third protein belonging to the group of proteins consisting of a first protein, a second protein, a third protein, a fourth protein and a fifth protein,
said first protein comprising the amino acid sequence as set forth in SEQ ID NO: 1,
said second protein comprising the amino acid sequence as set forth in SEQ ID NO: 2,
said third protein comprising the amino acid sequence as set forth in SEQ ID NO: 3,
said fourth protein comprising the amino acid sequence as set forth in SEQ ID NO: 4,
said fifth protein comprising the amino acid sequence as set forth in SEQ ID NO: 5,
b) comparing the amount of each of said at least one first protein, one second protein and one third protein with the amount of the same proteins in a biological sample of the same nature originating from a healthy individual not afflicted by a central nervous system disease, to establish the respective protein expression level ratios for each of said at least one first protein, one second protein and one third protein, and
c) diagnosing said individual as having:
(i) multiple sclerosis for the ratios of established in step b):
(1) for said at least first protein is higher than, or equal to, 2,
(2) for said at least second protein is higher than, or equal to, 2.5, and
(3) for said at least third protein is higher than, or equal to, 1.5,

(ii) multiple sclerosis or an inflammatory neurological disease for the ratio established in step b) for said at least the second protein is higher than, or equal to, 2; or
(iii) a clinically isolated syndrome without conversion to multiple sclerosis, a clinically isolated syndrome with conversion to multiple sclerosis, relapsing-remitting multiple sclerosis, primary progressive multiple sclerosis, a non inflammatory neurological disease, an inflammatory neurological disease or peripheral inflammatory neurological disease for the ration established in step b) for said at least third protein is higher than, or equal to, 1.5.

7. The method according to claim 6 , said method comprising:
a) measuring the amount of the first protein, the second protein, the third protein, the fourth protein and the fifth protein,
b) comparing the amount of the first protein, the second protein the third protein, the fourth protein and the fifth protein with the amount of the same proteins in a biological sample of the same nature originating from a healthy individual not afflicted by a central nervous system disease, to establish the respective protein expression level ratio for each of the first protein, the second protein, the third protein, the fourth protein and the fifth protein, and
c) diagnosing said individual as having:
(iv) multiple sclerosis for the ratio established in step b) for each of the first protein, the second protein, the third protein, the fourth protein and the fifth protein is higher than, or equal to, 2,
(v) multiple sclerosis or an inflammatory neurological disease for the ratio established in step b) for the second protein, is higher than, or equal to, 2.5,
(vi) multiple sclerosis, a non inflammatory neurological disease, an inflammatory neurological disease or peripheral inflammatory neurological disease for the ratio established in step b) for the third protein is higher than, or equal to, 1.5, and
(vii) an inflammatory neurological disease for the ratio established in step b) for the fourth protein is higher than, or equal to, 1.5.

8. The method according to claim 6 , wherein in step c) diagnosing said individual as having an inflammatory neurological disease radiologically isolated syndrome with conversion to multiple sclerosis, a clinically isolated syndrome without conversion to multiple sclerosis, a clinically isolated syndrome with conversion to multiple sclerosis, relapsing-remitting multiple sclerosis or primary progressive multiple sclerosis for the ratio established for the third protein is higher than, or equal to, 3.

9. The method according to claim 6 , wherein in step c) diagnosing said individual as having multiple sclerosis for the ratio established for the second protein is higher than, or equal to, 5.

10. The

Assignees

• Centre Nat Rech Scient
• Institut National De La Sante Et De La Rech Medical Inserm
• Univ Montpellier
• Centre Hospitalier Univ De Nimes

Inventors

• Thouvenot Eric
• Marin Philippe
• Urbach Serge
• Hinsinger Geoffrey

Classifications

• G01N2800/285

  Demyelinating diseases; Multipel sclerosis · CPC title

• G01N2333/978

  acting on carbon to nitrogen bonds other than peptide bonds (3.5) · CPC title

• G01N2333/82

  Translation products from oncogenes · CPC title

• G01N2333/70578

  NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30 CD40 or CD95 · CPC title

• G01N2333/4722

  Proteoglycans, e.g. aggreccan · CPC title