Biomarker composition for diagnosing stroke or post-stroke neurological damage, for diagnosing the severity of stroke or post-stroke neurological damage, and for predicting stroke prognosis

Patent metadata

Field	Value
Publication number	US-2026002211-A1
Application number	US-202418945687-A
Country	US
Kind code	A1
Filing date	Nov 13, 2024
Priority date	Jun 26, 2024
Publication date	Jan 1, 2026
Grant date	—

Abstract

The present invention relates to a biomarker composition for diagnosing stroke or post-stroke neurological damage, for diagnosing the severity of stroke or post-stroke neurological damage, and for predicting stroke prognosis, and the like. Using an ischemic stroke mouse disease model, a tissue damage analysis and a behavioral analysis were performed, and the mRNA level expression was confirmed, and as a result, Prox1 or Dcx could be selected as a biomarker. In addition, it was confirmed that the expression of Prox1 or Dcx increased as the severity of stroke or post-stroke neurological damage was higher, and thus the present invention is expected to be useful for diagnosing stroke or post-stroke neurological damage, for diagnosing the severity of stroke or post-stroke neurological damage, and for predicting stroke prognosis.

First claim

What is claimed is:

1 . A method of diagnosing stroke or post-stroke neurological damage, comprising:
(a) measuring the expression level of one or more mRNAs selected from the group consisting of Prox1 and Dex from a biological sample isolated from a subject; (b) comparing the expression level of the mRNAs with that of a control biological sample; (c) determining that the subject has a stroke or post-stroke neurological damage when the mRNA level of Prox1 is at least 2.03±0.64 as measured in Step (b); or determining that the subject has a stroke or post-stroke neurological damage when the mRNA level of DCX is at least 1.63±0.58 as measured in Step (b); and (d) treating the subject determined to have a stroke or post-stroke neurological damage in Step (c) by administering a pharmaceutically effective amount of a preparation for treating the subject.

2 . The method of claim 1 , wherein the stroke is one or more selected from the group consisting of hemorrhagic stroke and ischemic stroke.

3 . The method of claim 1 , wherein the stroke or post-stroke neurological damage is characterized by any one or more selected from the group consisting of:
(a) occurrence of a symptom of decreased blood flow reperfusion; (b) occurrence of a symptom of increased cerebral infarction area; (c) occurrence of a general motor impairment symptom; (d) occurrence of a sensorimotor impairment symptom; (e) occurrence of long-term cognitive memory impairment; and (f) occurrence of death or arrangement atrophy of hippocampal cells.

4 . The method of claim 1 , wherein the stroke or post-stroke neurological damage is characterized by an increase of mRNA level of any one or more selected from the group consisting of:
vascular cell adhesion molecule 1 (Vcam1), intercellular adhesion molecule 1 (Icam1), interleukin-1 beta (IL-1β), monocyte chemoattractant protein 1 (Mcp1), and C-C chemokine receptor 2 (Ccr2).

5 . The method of claim 1 , wherein the stroke or post-stroke neurological damage is due to cerebral artery occlusion.

6 . The method of claim 5 , wherein the cerebral artery is any one or more selected from the group consisting of anterior cerebral artery, middle cerebral artery, and posterior cerebral artery.

7 . The method of claim 1 , wherein the expression level of the mRNA is measured by any one or more methods selected from the group consisting of RT-PCR, competitive RT-PCR, real-time quantitative RT-PCR, multiplex reverse transcription polymerase chain reaction (Multiplex PCR), real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), RNase protection methods, Northern blotting, DNA chip technology assay, methylated DNA binding domain sequencing (MBDseq) analysis, and reduced representation bisulfite sequencing (RRBS) analysis.

8 . A method of treating stroke or post-stroke neurological damage, comprising:
(a) measuring the expression level of one or more mRNAs selected from the group consisting of Prox1 and Dcx from a biological sample isolated from a subject; (b) comparing the expression level of the mRNAs with that of a control biological sample; (c) determining that the severity of stroke or post-stroke neurological damage is high when the mRNA level of Prox1 is at least 2.03±0.64 as measured in Step (b); or determining that the severity of stroke or post-stroke neurological damage is high when the mRNA level of DCX is at least 1.63±0.58 as measured in Step (b); and (d) treating the subject determined to have high severity of stroke or post-stroke neurological damage in Step (c) by administering a pharmaceutically effective amount of a preparation for treating the subject.

9 . A method of treating stroke or post-stroke neurological damage, comprising:
(a) measuring the expression level of one or more mRNA selected from the group consisting of Prox1 and Dex or a gene encoding the protein from a biological sample isolated from an individual; (b) comparing the expression level of the mRNA with that of a control biological sample; (c) determining that the stroke is high when the mRNA level of Prox1 is at least 2.03±0.64 as measured in Step (b); or determining that stroke is high when the mRNA level of DCX is at least 1.63±0.58 as measured in Step (b); and (d) treating the subject determined to have a stroke or post-stroke neurological damage in Step (c) by administering a pharmaceutically effective amount of a preparation for treating the subject.

10 . The method of claim 9 , wherein the stroke is one or more selected from the group consisting of hemorrhagic stroke and ischemic stroke.

11 . The method of claim 9 , wherein the stroke or post-stroke neurological damage is characterized by any one or more selected from the group consisting of:
(a) occurrence of a symptom of decreased blood flow reperfusion; (b) occurrence of a symptom of increased cerebral infarction area; (c) occurrence of a general motor impairment symptom; (d) occurrence of a sensorimotor impairment symptom; (e) occurrence of long-term cognitive memory impairment; and (f) occurrence of death or arrangement atrophy of hippocampal cells.

12 . The method of claim 9 , wherein the stroke or post-stroke neurological damage is characterized by an increase of mRNA level of any one or more selected from the group consisting of:
vascular cell adhesion molecule 1 (Vcam1), intercellular adhesion molecule 1 (Icam1), interleukin-1 beta (IL-1β), monocyte chemoattractant protein 1 (Mcp1), and C-C chemokine receptor 2 (Ccr2).

13 . The method of claim 9 , wherein the stroke or post-stroke neurological damage is due to cerebral artery occlusion.

14 . The method of claim 13 , wherein the cerebral artery is any one or more selected from the group consisting of anterior cerebral artery, middle cerebral artery, and posterior cerebral artery.

15 . The method of claim 9 , wherein the expression level of the mRNA is measured by any one or more methods selected from the group consisting of RT-PCR, competitive RT-PCR, real-time quantitative RT-PCR, multiplex reverse transcription polymerase chain reaction (Multiplex PCR), real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), RNase protection methods, Northern blotting, DNA chip technology assay, methylated DNA binding domain sequencing (MBDseq) analysis, and reduced representation bisulfite sequencing (RRBS) analysis.

Assignees

• Catholic Univ Korea Ind Academic Cooperation Foundation

Inventors

• Oh Jae Sang
• Lee Dong-Hun
• Lee Eunchae

Classifications

• C12Q2600/158

  Expression markers · CPC title

• C12Q2600/112

  Disease subtyping, staging or classification · CPC title

• C12Q1/6883 Primary

  for diseases caused by alterations of genetic material · CPC title

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title

• G01N2800/2871

  Cerebrovascular disorders, e.g. stroke, cerebral infarct, cerebral haemorrhage, transient ischemic event · CPC title