BIOMARKERS FOR STROKE

• US 20120040858A1
• Filed: 08/05/2011
• Published: 02/16/2012
• Est. Priority Date: 08/13/2010
• Status: Abandoned Application

• Current Assignee: Morehouse School of Medicine
• Original Assignee: Morehouse School of Medicine
• Inventors: FORD, Byron D., Ford, Gregory
• Application Number:
  US13/204,358
• Publication Number:
  US 20120040858A1
• Time in Patent Office: Days
• US Class Current: 506/9
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2800/2871 Cerebrovascular disorders, e.g. stroke, cerebral infarct, cerebral haemorrhage, transient ischemic event
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 2800/56 Staging of a disease; Further complications associated with the disease
• CPC Class Codes: G01N 2800/60 Complex ways of combining multiple protein biomarkers for diagnosis
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

Biomarkers for stroke and methods for their detection are disclosed. In one aspect, the present application discloses biomarkers for the diagnosis of stroke in a subject. In another aspect, the application discloses a method for the diagnosis of stroke in a subject. The method comprises detection of stroke biomarkers in cerebrospinal fluid, blood, serum or PMBCs of a subject. Also disclosed is a kit for the detection of biomarkers for the diagnosis of stroke in a subject.

Claims

1. A method for diagnosing stroke in a subject comprising:

(a) measuring the level of one or more biomarkers in a sample from the subject;

(b) comparing the level of the one or more biomarkers to a reference level of the one or more biomarkers;

wherein the one or more biomarkers comprise gene products expressed from genes selected from the group consisting of IL-1α

, IL-1β

, IL-1ra, IL-3, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p40), IL-12(p70), IL-13, IL-15, IL-17, EGF, Eotaxin, FGF-2, FTL-3 ligand, Fractalkine, G-CSF, GM-CSF, GRO, IFN-α

2, IFN-γ

, IP-10, MCP-1, MCP-3, MCD, MIP-1α

, MIP-1β

, PDGF-aa, PGDF-aa bb, RANTES, sCD40L, sIL2-rα

, TNF-α

, TNF-β

, VEGF and genes listed in Tables 4, 5, 6 and 8.

2. The method of claim 1, wherein the one or more biomarkers are polynucleotides.

3. The method of claim 1, wherein the one or more biomarkers are peptides.

4. The method of claim 1, wherein step (a) includes measuring a panel of three or more biomarkers in the sample from the subject.

5. The method of claim 4, wherein the three or more biomarkers comprise expression product of at least one gene listed in Table 4, at least one gene listed in Table 5 and at least one gene listed in Table 6.

6. The method of claim 4, wherein the three or more biomarkers comprise

expression product of at least one gene selected from the group consisting of CD 163, PKC delta, pyruvate kinase, muscle (PKM2), thyroid hormone receptor associated protein 2, thyroid hormone receptor associated protein 5, nod-like receptor (NLR) family, pyrin domain containing 1, pancreatic ribonuclease (Rnase 1) and cytochrome b-245, beta polypeptide,

expression product of at least one gene selected from the group consisting of CD163, PKC delta, AKT1 substrate 1 (proline-rich) isoform 1, Cmtm3, WD repeat 19 (WDR19), alpha-2 type IX collagen, thyroid hormone receptor associated protein 2, thyroid hormone receptor associated protein 5, nod-like receptor (NLR) family, pyrin domain containing 1, pancreatic ribonuclease (Rnase 1), and complement factor H isoform a precursor;

and

expression product of at least one gene selected from the group consisting of NOD9 (NLRK1), aspartyl-tRNAsynthetase, lymphocyte cytosolic protein 1 (L-plastin), chitinase 1 (chitotriosidase), proteasome subunit alpha type 1(PSMA4), PKC delta, Cmtm3, WDR19, alpha-2 type IX collagen, PKM2, thyroid hormone receptor associated protein 2, thyroid hormone receptor associated protein 5, nod-like receptor family, pyrin domain containing 1, pancreatic ribonuclease (Rnase

     1), cytochrome b-245, beta polypeptide, and complement factor H isoform a precursor.

7. The method of claim 1, wherein step (a) includes measuring a panel of six or more biomarkers in the sample from the subject.

8. The method of claim 7, wherein the six or more biomarkers comprise expression product of at least two genes listed in Table 4, at least two genes listed in Table 5 and at least two genes listed in Table 6.

9. The method of claim 1, wherein step (a) includes measuring a panel of nine or more biomarkers in the sample from the subject.

10. The method of claim 9, wherein the nine or more biomarkers comprise expression product of at least three genes listed in Table 4, at least three genes listed in Table 5 and at least three genes listed in Table 6.

11. The method of claim 1, wherein step (a) includes measuring a panel of twenty or more biomarkers in the sample from the subject.

12. The method of claim 1 further comprising step (c) making a diagnosis based on the result of said comparing step (b).

13. The method of claim 1, wherein the sample is a body fluid sample or a tissue sample.

14. The method of claim 13, wherein the body fluid sample is a blood sample.

15. The method of claim 13, wherein the body fluid sample is a plasma or serum sample.

16. The method of claim 13, wherein the body fluid sample is a cerebrospinal fluid sample.

17. The method of claim 1, wherein the sample is peripheral blood mononuclear cells (PBMCs).

18. A method for determining disease progression in a subject after a stroke, comprising:

(a) measuring the level of one or more biomarkers in a first sample obtained from the subject at a first time point;

(b) measuring the level of the one or more biomarkers in a second sample obtained from the subject at a second time point;

(c) comparing the level of the one or more biomarkers at the first time point to the level of the one or more biomarkers at the second time point; and

(d) determining the disease progression between the first and the second time point based on the result of step (c),

wherein the one or more biomarkers comprise gene products expressed from genes selected from the group consisting of IL-1α

, IL-1β

, IL-1ra, IL-3, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p40), IL-12(p70), IL-13, IL-15, IL-17, EGF, Eotaxin, FGF-2, FTL-3 ligand, Fractalkine, G-CSF, GM-CSF, GRO, IFN-α

2, IFN-γ

, IP-10, MCP-1, MCP-3, MCD, MIP-1α

, MIP-113, PDGF-aa, PGDF-aa bb, RANTES, sCD40L, sIL2-rα

, TNF-α

, TNF-β

, VEGF and genes listed in Tables 4, 5, 6 and 8.

19. A method for determining the efficacy of a treatment for stroke in a subject, comprising:

(a) measuring the level of one or more biomarkers in a first sample obtained from the subject at a first time point;

(b) measuring the level of the one or more biomarkers in a second sample obtained from the subject at a second time point, wherein the subject is under treatment at the second time point;

(c) comparing the level of the one or more biomarkers at the first time point to the level of the one or more biomarkers at the second time point; and

(d) determining the efficacy of the treatment based on the result of step (c), wherein the one or more biomarkers comprise gene products expressed from genes selected from the group consisting of IL-1α

, IL-1β

, IL-1ra, IL-3, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p40), IL-12(p70), IL-13, IL-15, IL-17, EGF, Eotaxin, FGF-2, FTL-3 ligand, Fractalkine, G-CSF, GM-CSF, GRO, IFN-α

2, IFN-γ

, IP-10, MCP-1, MCP-3, MCD, MIP-1α

, MIP-1β

, PDGF-aa, PGDF-aa bb, RANTES, sCD40L, sIL2-rα

, TNF-α

, TNF-β

, VEGF, NMDA receptor, neuronal specific enolase, GFAP, Apo C-III, MMP-9, D-dimer, CRP, brain natriuretic peptide, S100B and genes listed in Tables 4, 5, 6 and 8.

20. A kit for detecting biomarkers for stroke in a biological sample, comprising:

(a) reagents for detecting a panel of biomarkers for stroke, and

(b) a instruction listing the reference range for each of the biomarkers,

wherein the panel of biomarkers comprise two or more biomarkers, and wherein the two or more biomarkers comprise gene products expressed from genes selected from the group consisting of IL-1α

, IL-1β

, IL-1ra, IL-3, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p40), IL-12(p70), IL-13, IL-15, IL-17, EGF, Eotaxin, FGF-2, FTL-3 ligand, Fractalkine, G-CSF, GM-CSF, GRO, IFN-α

2, IFN-γ

, IP-10, MCP-1, MCP-3, MCD, MIP-1α

, MIP-1β

, PDGF-aa, PGDF-aa bb, RANTES, sCD40L, sIL2-rα

, TNF-α

, TNF-β

, VEGF, NMDA receptor, neuronal specific enolase, GFAP, Apo C-III, MMP-9, D-dimer, CRP, brain natriuretic peptide, S100B and genes listed in Tables 4, 5, 6 and 8.