SAA-HDL Complex Temperature Control for Inflammation

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Solution Overview

Problem

Current treatments for conditions characterized by dysregulated inflammation, such as sepsis and autoinflammatory diseases, have limited success in addressing the underlying inflammatory response, leading to severe complications and high mortality.

Innovation Solution

The use of recombinant serum amyloid A proteins (rSAAs) and native serum amyloid A proteins (SAAs) in combination with their natural carrier, high-density lipoprotein (HDL), where the SAA-HDL complex is manipulated by temperature to either bind SAA and induce hypothermia for suppressed inflammation or release SAA and induce hyperthermia for excessive inflammation, to regulate the inflammatory response.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If SAA is administered to treat excessive inflammation, then anti-inflammatory effect is improved, but risk of inducing amyloidosis increases

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidamyloidosis risk

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

HDL is used as an intermediary carrier to transport SAA through the bloodstream. The HDL-SAA complex allows SAA to reach inflammatory sites without directly interacting with tissue in a way that would trigger amyloid deposition. HDL acts as a protective mediator that enables SAA's anti-inflammatory function while preventing its harmful amyloidogenic effect.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the physical-chemical parameters of SAA by complexing it with HDL. This parameter change (forming a lipoprotein complex) fundamentally alters SAA's behavior in vivo, preventing amyloid fibril formation while maintaining its ability to modulate inflammation. The complexation changes SAA's solubility, stability, and tissue interaction properties.

Inventive Principle:

Principle #35Parameter changes

2Object-affected harmful factors

If SAA binding to HDL is enhanced to reduce amyloidosis risk, then safety is improved, but availability of free SAA for anti-inflammatory action decreases

Engineering Contradiction:

Improveamyloidosis preventionVSAvoidanti-inflammatory efficacy

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The HDL-SAA complex is designed to be dynamic rather than static. The complex allows for controlled exchange of SAA between HDL and tissue sites, enabling SAA to be released where needed for anti-inflammatory action while maintaining overall complex stability to prevent amyloidosis. This dynamic equilibrium resolves the contradiction between binding strength and functional availability.

Inventive Principle:

Principle #15Dynamics

3Adaptability or versatility

If temperature is used to control SAA-HDL binding, then targeted treatment is improved, but treatment complexity increases

Engineering Contradiction:

Improvetargeted treatment capabilityVSAvoidtemperature control system

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The HDL-SAA complex system is designed to respond automatically to physiological temperature changes without requiring external control mechanisms. When body temperature increases during inflammation, the complex naturally adjusts its binding properties, allowing SAA release at the inflammatory site. The system serves itself by utilizing the body's own temperature signals to guide targeted treatment.

Inventive Principle:

Principle #25Self-service

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

This approach effectively modulates the inflammatory response by binding SAA to HDL at lower temperatures and releasing it at higher temperatures, providing a targeted treatment for dysregulated inflammation, thereby improving outcomes in conditions like sepsis and autoinflammatory diseases.

Implementation Method 1

binding SAA to HDL at actively inducing normal temperature or graded hypothermia

Methodology Applied

Scientific EffectTemperature-dependent binding:

Implementation Method 2

separating the SAAs-HDL complex, wherein said step also includes actively inducing gradual hyperthermia in the subject

Methodology Applied

Scientific EffectTemperature-dependent release:

Data Source

PatentUS20230087385A1Use of SAA, rSAA or inhibitors of SAA in the treatment of dysregulated inflammation

Publication Date: 2023.03.23 LINKE REINHOLD

AI summary

The present invention describes use of recombinant serum amyloid A proteins (rSAAs) and native serum amyloid A proteins (SAAs) with their natural carrier and an inhibitor of SAA, particularly high density lipoprotein (HDL), in the treatment of a condition or disease that are characterized by dysregulated inflammation. Thereby, in case of dysregulated inflammation with an excessive inflammation, the function of rSAAs and SAAs may be inactivated by binding SAA to HDL at inducing normal temperature or graded hypothermia, leading to an increased amount of SAAs-HDL-complex in said subject in vivo, and reversely in case of dysregulated inflammation which has led to low temperatures and hypothermia (suppressed inflammation), rSAA may be administered and/or the SAA level may be increased by separating the SAAs-HDL complex, wherein said step also includes inducing gradual hyper-thermia in the subject.