Biomarkers for diagnosis of stroke and its causes

a biomarker and stroke technology, applied in the field of biomarkers for diagnosis of stroke and its causes, can solve the problems of inability to diagnose stroke in a straightforward way, stroke remains unknown or cryptogenic, biomarkers of ischemic stroke subtype lack sufficient sensitivity and specificity to be used in clinical practice, etc., to achieve high throughput screening and enhance activation or enzymatic activity

Inactive Publication Date: 2012-03-15
RGT UNIV OF CALIFORNIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0109]“Inhibitors,”“activators,” and “modulators” of expression or of activity are used to refer to inhibitory, activating, or modulating molecules, respectively, identified using in vitro and in vivo assays for expression or activity, e.g., ligands, agonists, antagonists, and their homologs and mimetics. The term “modulator” includes inhibitors and activators Inhibitors are agents that, e.g., inhibit expression of a polypeptide or polynucleotide of the invention or bind to, partially or totally block stimulation or enzymatic activity, decrease, prevent, delay activation, inactivate, desensitize, or down regulate the activity of a polypeptide or polynucleotide of the invention, e.g., antagonists. Activators are agents that, e.g., induce or activate the expression of a polypeptide or polynucleotide of the invention or bind to, stimulate, increase, open, activate, facilitate, enhance activation or enzymatic activity, sensitize or up regulate the activity of a polypeptide or polynucleotide of the invention, e.g., agonists. Modulators include naturally occurring and synthetic ligands, antagonists, agonists, small chemical molecules and the like. Assays to identify inhibitors and activators include, e.g., applying putative modulator compounds to cells, in the presence or absence of a polypeptide or polynucleotide of the invention and then determining the functional effects on a polypeptide or polynucleotide of the invention activity. Samples or assays comprising a polypeptide or polynucleotide of the invention that are treated with a potential activator, inhibitor, or modulator are compared to control samples without the inhibitor, activator, or modulator to examine the extent of effect. Control samples (untreated with modulators) are assigned a relative activity value of 100% Inhibition is achieved when the activity value of a polypeptide

Problems solved by technology

However, the diagnosis is not always straightforward, particularly in the acute setting where an accurate, inexpensive and rapid diagnosis is critical to optimally treat patients.
However, in many patients the cause of stroke remains unknown or cryptogenic in spite of extensive investigation.
However, biomarkers of ischemic stroke subtype currently lack sufficient sensitivity and specificity to be used in clinical practice.

Method used

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  • Biomarkers for diagnosis of stroke and its causes
  • Biomarkers for diagnosis of stroke and its causes
  • Biomarkers for diagnosis of stroke and its causes

Examples

Experimental program
Comparison scheme
Effect test

example 1

Biomarkers for the Diagnosis of the Occurrence and / or Risk of Ischemic Stroke

Materials and Methods

[0205]The study had two objectives: (1) Demonstrate that the previously identified 29 probes distinguish IS from healthy controls [Tang Y et al., J Cereb Blood Flow Metab., 26:1089-1102 (2006)] in a new cohort; and (2) Identify additional genes that discriminate IS from vascular risk factor (SAVVY) controls and myocardial infarction (MI) controls. Whole blood was drawn from IS patients (n=70, 199 samples) at ≦3, 5 and 24 hours (3 h IS, 5 h IS, 24 IS) as part of the CLEAR trial [Pancioli A M et al., Stroke, 39:3268-3276 (2008)] (NCT00250991 at Clinical-Trials.gov). IS subjects were treated with r-tPA with or without eptifibatide after the 3 h blood sample was obtained. Controls included healthy subjects (n=38), subjects with acute myocardial infarction (MI, n=17) and subjects with at least one cardiovascular risk factor (hypertension, diabetes mellitus, hyperlipidemia, or tobacco smoking...

example 2

Biomarkers for the Diagnosis of the Cause of Ischemic Stroke

1. Study Patients

[0237]Patients with acute ischemic stroke were enrolled from the CLEAR trial, a multicenter, randomized double-blind safety study of recombinant tissue-plasminogen activator (rt-PA) and eptifibatide as previously described [Pancioli A M et al., Stroke, 39:3268-3276 (2008)] (NCT00250991 at Clinical-Trials.gov). The institutional review board of each site approved the study protocol and written informed consent was obtained from each patient prior to study entry. Eligible patients had a diagnosis of acute ischemic stroke, therapy initiated within 3 hours of stroke onset, a National Institutes of Health Stroke Scale (NIHSS)>5, and were 18-80 years of age. All patients had standardized clinical evaluations, including NIHSS, and brain imaging. Blood samples were drawn into PAXgene tubes (PreAnalytiX, Hilden, Germany) at <3 hours, 5 hours, and 24 hours after stroke onset for use in gene expression analysis. A tot...

example 3

Exemplary Flow Outline of Using Gene Expression Analysis for the Diagnosis of the Occurrence of Ischemic Stroke and the Cause of Ischemic Stroke

[0266]The following example provides an exemplary outline of using the biomarkers described herein for the diagnosis of the occurrence and cause of stroke in a patient suspected of having a stroke.

[0267](1) Detection of biomarkers can be performed using a microarray, e.g., a microfluidics approach. cDNA from the patient's RNA in a blood sample is prepared and labeled (e.g., with a fluorophore). The labled cDNA is hybridized to probes on the array within the microfluidics device. The fluoresence of the bound cDNA is measured to provide a quantitative measure of the amount of RNA for each gene expressed in the blood of the patient.

[0268](2) The amount of RNA for at least about 15 target genes is first measured in the blood sample. The amount of RNA for at least about 30 endogenous reference biomarkers is measured in the blood sample. The amoun...

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Abstract

The present invention provides compositions and methods for the diagnosis of the occurrence and cause of stroke.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Application No. 61 / 364,449, filed on Jul. 15, 2010, the entire disclosure of which is hereby incorporated herein by reference for all purposes.STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT[0002]This invention was made with Government support under Grant No. NS056302, awarded by the National Institutes of Health and National Institute of Neurological Disorders and Stroke (NINDS) and Grant No. 077501 4N, awarded by the American Heart Association. The government has certain rights in this invention.FIELD OF THE INVENTION[0003]The present invention provides compositions and methods for diagnosing stroke and the risk of stroke, as well as the cause of stroke.BACKGROUND OF THE INVENTION[0004]Stroke is a leading cause of adult death and disability [Thom T et al., Circulation, 113:e85-151 (2006); WHO, The atlas of heart disease and stroke (2005)...

Claims

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Application Information

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IPC IPC(8): C40B30/04C12Q1/68C40B40/06
CPCC12Q1/6883C12Q2600/158C12Q2600/16G01N2800/2871G01N2800/50G01N33/6896
InventorSHARP, FRANKSTAMOVA, BORYANAJICKLING, GLEN C.
OwnerRGT UNIV OF CALIFORNIA