Monocyte Metabolic Phenotyping for Mitochondrial Dysfunction Detection

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Solution Overview

Problem

Current methods lack sensitivity and accuracy in detecting and diagnosing diseases characterized by mitochondrial dysfunction, particularly in conditions such as ischemia, stroke, and neurodegenerative diseases, using monocytes as indicators of mitochondrial dysfunction.

Innovation Solution

A method involving the analysis of activated monocyte levels, ratios, and biomarkers in biological samples to identify mitochondrial dysfunction, including the use of aromatic-cationic peptides to assess therapeutic efficacy, utilizing techniques like flow cytometry and bioenergetic assays.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current diagnostic methods are used to detect mitochondrial dysfunction, then the diagnostic process is simple, but the sensitivity and accuracy of detection are insufficient

Engineering Contradiction:
Improvedetection sensitivityVSAvoidmethod complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent uses monocytes as intermediary cells to detect mitochondrial dysfunction. Instead of directly measuring mitochondrial function in affected tissues, the method measures metabolic markers (such as ATP levels, oxidative phosphorylation activity) in monocytes circulating in the blood. These monocytes serve as a surrogate indicator, reflecting systemic mitochondrial dysfunction with high sensitivity while avoiding complex tissue biopsies or direct mitochondrial measurements.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces complex invasive diagnostic procedures with simpler blood-based metabolic assays. Instead of mechanical tissue sampling or complex imaging, the method uses biochemical measurements (metabolic phenotyping) of monocytes in peripheral blood, substituting mechanical/invasive approaches with chemical/biochemical detection methods that are less invasive and more sensitive.

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

2Measurement precision

If invasive diagnostic procedures are used to assess mitochondrial dysfunction, then detection accuracy improves, but patient discomfort and procedural complexity increase

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidprocedure simplicity
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent employs monocytes as a surrogate marker system. Rather than directly assessing mitochondrial function in affected organs through invasive procedures, the method measures metabolic parameters in circulating monocytes that reflect systemic mitochondrial dysfunction. This intermediary approach achieves high diagnostic accuracy through simple blood draws and metabolic assays, eliminating the need for invasive tissue sampling or complex procedural interventions.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent leverages the natural physiological role of monocytes as sentinels of inflammation and metabolic stress. Monocytes naturally respond to mitochondrial dysfunction by altering their metabolic phenotype, which can be detected through standard metabolic assays. The body's own immune cells perform the diagnostic function, eliminating the need for external invasive procedures to obtain diagnostic information.

Inventive Principle:
Principle #25Self-service

3Measurement precision

If traditional metabolic assays are used, then the assay procedure is straightforward, but the ability to detect early mitochondrial dysfunction is limited

Engineering Contradiction:
Improveearly detection capabilityVSAvoidassay complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent performs metabolic phenotyping of monocytes as a preliminary diagnostic step before clinical symptoms fully develop. By measuring metabolic markers (ATP production, oxidative phosphorylation capacity) in circulating monocytes, the method can detect early mitochondrial dysfunction and metabolic reprogramming before tissue damage occurs or clinical manifestations appear, enabling early intervention.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent monitors dynamic changes in metabolic parameters of monocytes rather than static endpoints. By tracking changes in ATP levels, oxidative phosphorylation activity, and other metabolic markers over time or in response to stimuli, the method detects subtle early alterations in mitochondrial function that precede overt disease, using sensitive metabolic assays that can resolve small parameter changes.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS11366104B2Methods of identifying and monitoring mitochondrial dysfunction using monocyte screening
Publication Date: 2022.06.21 STEALTH BIOTHERAPEUTICS INC
  • US11366104B2 patent drawing
  • US11366104B2 patent drawing
  • US11366104B2 patent drawing

AI summary

The present technology provides methods for detecting and diagnosing diseases and conditions characterized by mitochondrial dysfunction using monocytes as an indicator of the dysfunction.