Cellular fibronectin as a diagnostic marker in stroke and methods of use thereof

• US 7,634,360 B2
• Filed: 01/29/2005
• Issued: 12/15/2009
• Est. Priority Date: 09/23/2003
• Status: Expired due to Fees

• Current Assignee: Prediction Sciences LLC
• Original Assignee: Prediction Sciences LLC
• Inventors: Castillo, Jose, Castellanos, Mar (St. Feliu De Guixols, Diamond, Cornelius Allen, Davalos, Antoni
• Primary Examiner(s): BORIN, MICHAEL L
• Application Number:
  US11/046,592
• Publication Number:
  US 20050130230A1
• Time in Patent Office: 1,781 Days
• Field of Search: None
• US Class Current: 702/19
• CPC Class Codes: G01N 2333/78 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
• CPC Class Codes: G01N 2800/2871 Cerebrovascular disorders, e.g. stroke, cerebral infarct, cerebral haemorrhage, transient ischemic event
• CPC Class Codes: G01N 33/6848 Methods of protein analysis involving mass spectrometry
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere
• CPC Class Codes: G16B 20/00 ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• CPC Class Codes: G16B 20/20 Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• CPC Class Codes: G16B 40/00 ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• CPC Class Codes: G16B 40/10 Signal processing, e.g. from mass spectrometry [MS] or from PCR
• CPC Class Codes: G16B 40/20 Supervised data analysis
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

The present invention relates to methods for the diagnosis and evaluation of stroke and stroke sub-type. A variety of bio-markers are disclosed for assembling a panel for such diagnosis and evaluation. Methods are disclosed for selecting markers and correlating their combined levels with a clinical outcome of interest. In various aspects: the invention provides methods for early detection and differentiation of stroke subtypes, for determining the prognosis of a patient presenting with stroke symptoms, and identifying a patient at risk for hemorrhagic transformation after thrombolyic therapy. Methods are disclosed that provide rapid, sensitive and specific assays to greatly increase the number of patients that can receive beneficial stroke treatment and therapy, and reduce the costs associated with incorrect stroke diagnosis.

Claims

1. A method of determining presence or risk of hemorrhage in a human patient, said method comprising:

obtaining a test sample from the patient, wherein the sample is a plasma sample;

forming a complex between an antibody probe to cellular fibronectin (c-Fn) and c-Fn present in the test sample;

measuring the amount of the complex formed and determining the amount of c-Fn in the sample; and

determining the presence of or future risk for hemorrhage in the patient when the level of c-Fn in the test sample is greater than 3.6 μ

g/mL

2. The method according to claim 1, wherein determining the risk of hemorrhage occurs following administration thrombolytic therapy.

3. The method according to claim 2, further comprising:

determining the patient'"'"'s risk of hemorrhage following thrombolytic therapy from said measured level of c-Fn; and

administering a stroke therapy.

4. The method according to claim 3, where the risk of hemorrhage following thrombolytic therapy is risk of a parenchymal hemorrhage.

5. The method according to claim 3, where the risk of hemorrhage following thrombolytic therapy is risk of a parenchymal hemorrhage and the level of c-Fn in the patient'"'"'s plasma is greater than 5.8 μ

g/mL.

6. The method according to claim 3, where the risk of hemorrhage following thrombolytic therapy is risk of a hemorrhagic infarction type 2.

7. The method according to claim 1, further comprising analyzing the obtained test sample for the proteomic marker MMP-9;

and

correlating the analyzed amount of the proteomic marker MMP-9 and the presence or amount of said c-Fn in order to determine the present or future risk of a hemorrhage for the subject.

8. A method of determining risk of hemorrhage transformation in a human patient receiving tissue plasminogen activator therapy for ischemic stroke, comprising:

identifying a patient suffering from ischemic stroke;

providing the patient with tissue plasminogen activator (t-PA) therapy;

obtaining a test sample from the patient, wherein the sample is a plasma sample;

forming a complex between an antibody probe against cellular fibronectin (c-Fn) and c-Fn present in the test sample;

measuring the amount of the complex formed and determining the amount of c-Fn in the sample; and

determining the presence of or future risk for hemorrhage transformation in the patient when the level of c-Fn in the test sample is greater than 3.6 μ

g/mL.

9. The method according to claim 8, wherein the risk of hemorrhage transformation following thrombolytic therapy is risk of a parenchymal hemorrhage.

10. The method according to claim 9, wherein the level of c-Fn in the patient'"'"'s plasma is greater than 5.8 μ

g/mL.

11. The method according to claim 8, where the risk of hemorrhage following thrombolytic therapy is risk of a hemorrhagic infarction type 2.