AIM Protein Neutralizes DAMPs to Suppress Sterile Inflammation

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Solution Overview

Problem

Current therapies for ischemic diseases, such as cerebral infarction, do not effectively address sterile inflammation caused by the release of damage-associated molecular patterns (DAMPs), leading to inadequate prognosis for stroke patients.

Innovation Solution

The use of an apoptosis inhibitor of macrophage (AIM) or its fragments, which bind to various DAMPs, neutralizing their biological activity and promoting efficient phagocytosis and removal by microglia and macrophages, thereby suppressing sterile inflammation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional therapies (thrombolysis and thrombectomy) are used for ischemic stroke, then acute blood flow restoration is achieved, but sterile inflammation and DAMP release continue to worsen the prognosis

Engineering Contradiction:

ImproveprognosisVSAvoidsterile inflammation

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent converts the harmful effect of DAMP release into a beneficial process by using AIM protein to bind to DAMPs and facilitate their phagocytosis. The DAMPs, which normally drive harmful sterile inflammation, are instead captured and removed by microglia and macrophages through AIM-mediated mechanisms, transforming the harmful inflammatory signal into a controlled clearance process that reduces neurotoxicity and improves prognosis.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

AIM protein serves as an intermediary molecule between DAMPs and phagocytes. It binds to DAMPs and presents them to phagocytic cells, enhancing the engulfment process. This intermediary mechanism allows for targeted removal of harmful DAMPs while controlling the inflammatory response, thereby improving prognosis without exacerbating sterile inflammation.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If DAMPs are released from necrotic cells, then cell debris is cleared, but intracellular inflammatory agents are released into the extracellular environment

Engineering Contradiction:

Improvedead cell removalVSAvoidinflammatory cytokines

Core Design Contradiction:

ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent transforms the harmful release of inflammatory agents into a controlled process. AIM protein binds to DAMPs and facilitates their targeted phagocytosis by microglia and macrophages, converting the uncontrolled release of inflammatory cytokines into a regulated clearance mechanism that removes debris while minimizing inflammation.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent enhances the self-service capability of phagocytes. AIM protein is internalized by phagocytes via multiple scavenger receptors, equipping them with enhanced ability to recognize and engulf DAMPs. This self-service mechanism allows phagocytes to autonomously clear debris and regulate inflammation without external intervention, improving both productivity and reducing harmful factors.

Inventive Principle:

Principle #25Self-service

3Productivity

If AIM binds to DAMPs, then phagocytosis and removal of dead cell debris is enhanced, but the complexity of the therapeutic mechanism increases

Engineering Contradiction:

Improvedebris clearance efficiencyVSAvoidmechanism complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

AIM protein exhibits multi-functionality, serving both as a binder for DAMPs and as an enhancer of phagocytosis. It simultaneously performs multiple functions: binding to various DAMPs (PRDX, HMGB1, S100 proteins), facilitating their internalization by phagocytes, and enhancing debris clearance efficiency. This multi-functional approach improves productivity without proportionally increasing mechanism complexity.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

AIM acts as a simple intermediary protein that bridges DAMPs and phagocytes. Its mechanism relies on basic binding interactions and receptor-mediated internalization, avoiding complex signaling pathways or multiple drug combinations. This intermediary approach enhances debris clearance efficiency through a relatively simple and straightforward mechanism.

Inventive Principle:

Principle #24Intermediary (Mediator)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

AIM effectively reduces the levels of DAMPs in the infarcted region, suppresses inflammation, and enhances the removal of dead cell debris, thereby improving the prognosis for ischemic diseases such as cerebral infarction.

Implementation Method 1

This cluster develops charge-based interactions with dead cells, whose surface is strongly negatively charged due to the high levels of exposed phosphatidylserine

Methodology Applied

Scientific EffectCharge-based interactions: Electrostatics

Implementation Method 2

AIM is highly internalized by phagocytes via multiple scavenger receptors

Methodology Applied

Scientific EffectEndocytosis: Absorption (physical)

Data Source

PatentUS20250108090A1Therapeutic agent for ischemic disease

Publication Date: 2025.04.03 MIYAZAKI TORU

AI summary

The present invention provides an agent for treating an ischemic disease, including an apoptosis inhibitor of macrophage (AIM), an AIM fragment having a biological activity of AIM, or a nucleic acid encoding the AIM or AIM fragment.