Aromatic Cationic Peptide for Left Ventricular Remodeling Reversal

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Solution Overview

Problem

Current treatments for heart failure, particularly in the form of left ventricular remodeling, are inadequate in addressing the underlying metabolic and functional abnormalities that contribute to the progression of the condition, leading to increased oxygen demand and eventual congestive heart failure.

Innovation Solution

The use of D-Arg-2',6'-Dmt-Lys-Phe-NH2 peptide to normalize levels of C-reactive protein, interleukin-6, tumor necrosis factor-alpha, reactive oxygen species, and brain natriuretic peptide, while increasing Taz1 expression and mitochondrial K ATP activity, thereby stabilizing and enhancing the function of remaining viable myocardium.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments for heart failure are used, then some symptomatic relief may be achieved, but the underlying metabolic and functional abnormalities are not addressed, leading to increased oxygen demand and progression to congestive heart failure

Engineering Contradiction:
Improveeffectiveness of treatmentVSAvoidincreased oxygen demand
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent extracts and targets specific pathological mechanisms (inflammatory markers, oxidative stress, metabolic abnormalities) that drive heart failure progression. By isolating and addressing these specific factors through the peptide D-Arg-2',6'-Dmt-Lys-Phe-NH2 and associated therapies, the treatment removes the harmful drivers of disease progression rather than merely masking symptoms, thereby reducing oxygen demand while improving reliability.

Inventive Principle:
Principle #2Taking out (Extraction)

2Productivity

If the left ventricle dilates to compensate for reduced stroke volume, then stroke volume is initially maintained, but progressive dilatation and hypertrophy eventually lead to congestive heart failure

Engineering Contradiction:
Improvestroke volumeVSAvoidlong-term cardiac function
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent applies preliminary action by intervening early in the remodeling process to prevent the progression from compensatory dilation to decompensated failure. The peptide D-Arg-2',6'-Dmt-Lys-Phe-NH2 and associated therapies are administered to normalize metabolic and functional abnormalities before they lead to irreversible structural changes and congestive heart failure, thereby maintaining both stroke volume and long-term reliability.

Inventive Principle:
Principle #10Preliminary action

3Strength

If left ventricular remodeling progresses, then the heart attempts to compensate for myocardial loss, but this leads to increased wall stress and oxygen demand

Engineering Contradiction:
Improvecompensatory mechanismVSAvoidoxygen demand
Core Design Contradiction:
StrengthVSUse of energy by moving object

Solution Approach 1:

The patent changes key physiological parameters through the peptide D-Arg-2',6'-Dmt-Lys-Phe-NH2 and associated therapies. By normalizing inflammatory markers (C-reactive protein, interleukin-6, tumor necrosis factor-alpha), reducing oxidative stress (reactive oxygen species), and adjusting metabolic parameters (brain natriuretic peptide), the treatment modifies the remodeling process to maintain compensatory strength while reducing the excessive oxygen demand that would otherwise result.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP4397314B1Treatment of left ventricular remodeling
Publication Date: 2025.12.03 STEALTH BIOTHERAPEUTICS INC
  • EP4397314B1 patent drawingFigure 1
  • EP4397314B1 patent drawingFigure 2
  • EP4397314B1 patent drawingFigure 3

AI summary

The disclosure provides methods of preventing or treating heart failure in a mammalian subject, reducing risk factors associated with heart failure, and/or reducing the likelihood or severity of heart failure. The disclosure also provides methods of preventing, or treating LV remodeling in a mammalian subject, and/or reducing the likelihood or severity of LV remodeling. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide. In some embodiments, the methods comprise administering to the subject an effective amount of an aromatic cationic peptide to reduce levels of C-reactive protein, tumor necrosis factor alpha, interleukin 6, reactive oxygen species, Nt-pro BNP, and/or cardiac troponin I, and/or reduce expression levels of MLCL AT1 and/or ALCAT 1 in subjects in need thereof. In some embodiments, the methods comprise administering to the subject an effective amount of an aromatic cationic peptide to increase expression of Taz1 and/or increase mK ATP activity in subjects in need thereof.