Aromatic-Cationic Peptide Mitigates Burn Injury Hypermetabolism

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Solution Overview

Problem

Burn injuries result in systemic complications such as hypermetabolism, organ dysfunction, and skeletal muscle dysfunction due to the release of inflammatory mediators like ROS and RNS, leading to inflammation, immunosuppression, infection, and multiple organ failure, for which current treatments are inadequate in managing the secondary effects effectively.

Innovation Solution

Administration of an aromatic-cationic peptide, specifically D-Arg-2'6'-dimethyltyrosine-Lys-Phe-NH2, which penetrates cell membranes, reduces oxidative stress, and increases ATP synthesis rate by recovering mitochondrial redox status and enhancing the expression of peroxisome proliferator activated receptor-gamma coactivator-1β (PGC-1β), thereby addressing the systemic and local pathophysiological effects of burn injuries.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If aggressive burn wound excision techniques and graft therapy are used, then survival rates and clinical outcomes improve, but the complexity of treatment and risk of secondary complications increase

Engineering Contradiction:

Improvesurvival rateVSAvoidtreatment complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The aromatic-cationic peptide acts as an intermediary substance that mediates between the burn injury and the body's physiological response. It specifically targets and neutralizes ROS and RNS without interfering with surgical excision or grafting procedures, thereby improving outcomes while avoiding increased treatment complexity

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the biochemical parameter of oxidative stress by introducing a peptide that specifically scavenges ROS and RNS. This parameter change (reducing oxidative stress) leads to improved survival rates without requiring changes to the physical treatment protocol

Inventive Principle:

Principle #35Parameter changes

2Reliability

If free radical production is increased to enhance antimicrobial action and wound healing, then infection resistance improves, but tissue damage and inflammation worsen

Engineering Contradiction:

Improveantimicrobial efficacyVSAvoidtissue damage

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The peptide exhibits local quality by specifically targeting different types of reactive species at different locations. It selectively scavenges harmful ROS and RNS in systemic circulation while allowing beneficial free radicals at the wound site to maintain their antimicrobial and healing functions

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The invention converts the harmful effect of excessive ROS and RNS production into a benefit by using the same free radical mechanism that provides antimicrobial action. The peptide harnesses the body's natural free radical production for good while neutralizing the harmful excess, transforming a double-edged sword into a controlled tool

Inventive Principle:

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

3Ease of operation

If conventional burn treatments are administered, then immediate wound care is provided, but secondary complications such as hypermetabolism and organ dysfunction are not effectively managed

Engineering Contradiction:

Improvewound care efficiencyVSAvoidmanagement of secondary complications

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The aromatic-cationic peptide provides multi-functionality by simultaneously addressing multiple secondary complications. It reduces hypermetabolism, protects organs from oxidative damage, prevents immunosuppression, and reduces inflammation all through a single administered substance, making the treatment system universally effective against various post-burn complications

Inventive Principle:

Principle #6Universality (Multi-functionality)

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

The peptide effectively attenuates hypermetabolism, protects organs from damage, and improves mitochondrial function, reducing the severity of burn injuries and associated complications by enhancing ATP synthesis and mitigating oxidative stress.

Implementation Method 1

Mediators including Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) are increased in affected tissue, which are implicated in pathophysiological events observed in burn patients

Methodology Applied

Scientific EffectOxidative stress: Oxidation

Implementation Method 2

increases ATP synthesis rate by recovering mitochondrial redox status and enhancing the expression of peroxisome proliferator activated receptor-gamma coactivator-1β (PGC-1β)

Methodology Applied

Scientific EffectATP synthesis: Fermentation

Data Source

PatentEP3906933A1D-arg-2'6'-dimethyltyrosine-lys-phe-NH2 for use in the prevention of secondary complications of burn injuries

Publication Date: 2021.11.10 THE GENERAL HOSPITAL CORP

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AI summary

The disclosure relates to methods for treating a subject suffering from a burn injury or associated complications by administering to the subject an effective amount of an aromatic-cationic peptide. For example, a burn injury may be associated with distant pathophysiological effects, such as hypermetabolism, skeletal muscle dysfunction, and organ damage. The disclosure also relates to methods for protecting a subject from a burn injury by administering an effective amount of an aromatic-cationic peptide to a subject at risk of a burn injury.