Stroke Subtype Differentiation Using GFAP and RBP4 Biomarkers

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Solution Overview

Problem

Current methods for differentiating ischemic stroke from hemorrhagic stroke are limited by the availability and reliability of brain imaging technologies in primary hospitals, and existing biomarker-based tests are not sufficiently rapid or accurate for timely treatment initiation.

Innovation Solution

An in vitro method using a combination of glial fibrillary acidic protein (GFAP) and other biomarkers such as neurofilament medium polypeptide (NEF3), β-synuclein, and retinol binding protein 4 (RBP4) to differentiate between ischemic and hemorrhagic strokes, with specific reference values for determining appropriate therapies.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If brain imaging data by CT or MRI is used for stroke subtype diagnosis, then diagnostic accuracy is improved, but availability and accessibility deteriorate due to lack of resources in primary hospitals

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidavailability
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent extracts the diagnostic function from complex imaging equipment (CT/MRI) and transfers it to a simple blood test system. By identifying specific biomarkers (GFAP, S100B, RBP4, APOB, LPL) that can be measured in blood samples, the diagnostic capability is extracted from the imaging modality and embodied in a routine laboratory test that is widely available in primary hospitals.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces blood-based biomarkers as an intermediary between the patient's brain condition and the diagnostic result. Instead of directly imaging the brain with expensive equipment, the method uses biomarkers circulating in the blood as mediators that reflect the underlying brain pathology, enabling indirect but accurate diagnosis through accessible blood testing.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If brain imaging by CT or MRI is used for stroke differentiation, then diagnostic reliability is improved, but susceptibility to error increases when medical personnel are inexperienced or inadequately trained

Engineering Contradiction:
Improvediagnostic reliabilityVSAvoidinterpretation complexity
Core Design Contradiction:
ReliabilityVSDifficulty of detecting and measuring

Solution Approach 1:

The patent replaces the mechanical/operational system of image acquisition and interpretation (requiring skilled personnel to operate imaging equipment and analyze complex images) with a biochemical measurement system. The diagnostic process is substituted from visual/image-based interpretation to quantitative biomarker measurement, which can be automatically analyzed by laboratory systems without requiring specialized neurological interpretation skills.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent changes the diagnostic parameter from complex image patterns requiring expert interpretation to specific biochemical concentrations (biomarker levels) that can be objectively measured and compared against established reference ranges. This parameter transformation makes the diagnostic process more standardized and less dependent on individual operator expertise.

Inventive Principle:
Principle #35Parameter changes

3Productivity

If existing biomarker-based tests are used for stroke differentiation, then rapid diagnosis is achieved, but accuracy deteriorates compared to imaging methods

Engineering Contradiction:
Improvediagnosis speedVSAvoiddiagnostic accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent merges multiple biomarkers (GFAP, S100B, RBP4, APOB, LPL) into a combined diagnostic approach. By measuring several biomarkers simultaneously and integrating their information, the method achieves both the speed of laboratory testing and the accuracy previously requiring imaging. The combination of multiple biomarkers compensates for individual limitations and provides a more robust diagnostic signal.

Inventive Principle:
Principle #5Merging (Combining)

Data Source

PatentEP3227688B1Methods for differentiating ischemic stroke from hemorrhagic stroke
Publication Date: 2021.05.05 FUNDACIÓ HOSPITAL UNIVERSITARI VALL D HEBRON - INSTITUT DE RECERCA
  • EP3227688B1 patent drawingFigure 1
  • EP3227688B1 patent drawingFigure 1
  • EP3227688B1 patent drawingFigure 2

AI summary

The invention relates to a method for differentiating ischemic stroke from hemorrhagic stroke in a patient and to a method for selecting a patient suffering stroke for a therapy with an antithrombotic agent or with an agent capable of reducing blood pressure based on the determination of the level of GFAP in a sample of said patient in combination with one or more markers selected from the group consisting of NEF3, β-synuclein, CARNS1 and RBP4, or based on determining the level of RBP4 in a sample of said patient. Furthermore, the invention relates to a kit comprising a reagent for detecting the level of a marker selected from GFAP NEF3, β-synuclein, CARNS1, RBP4 or a combination thereof and to the use of the said kit in the methods of the invention.