MYDGF Protein Attenuates Cardiac Remodeling and Fibrosis

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Solution Overview

Problem

Current treatments lack effective means for addressing fibrosis, hypertrophy, and heart failure, particularly in conditions like chronic heart failure with preserved or reduced ejection fraction, and idiopathic pulmonary fibrosis, where existing therapies do not adequately manage fibrotic tissue formation and cardiac remodeling.

Innovation Solution

The use of myeloid-derived growth factor (MYDGF) protein or its variants, which inhibit transforming growth factor β1-stimulated SMAD phosphorylation and attenuate left ventricular remodeling, is proposed for treating or preventing fibrosis and hypertrophy, including heart failure by administering the protein or nucleic acids encoding MYDGF through vectors in host cells, thereby improving heart function.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing therapies are used for treating fibrosis and hypertrophy, then treatment coverage is limited, but therapeutic effectiveness is insufficient

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidtreatment coverage

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies universality by demonstrating that MYDGF protein can treat multiple different conditions (pulmonary fibrosis, cardiac fibrosis, hypertrophy, heart failure) through a single therapeutic agent. The protein inhibits TGF-β1 signaling pathway which is common to all these fibrotic and hypertrophic conditions, making it a multi-functional treatment that addresses various diseases with preserved or reduced ejection fraction through the same mechanism of action

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Reliability

If MYDGF is administered to treat fibrosis and hypertrophy, then therapeutic effectiveness improves, but mechanism complexity increases

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidmechanism complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies the extraction principle by isolating and utilizing the specific biological activity of MYDGF protein that inhibits TGF-β1-stimulated SMAD phosphorylation. Instead of addressing the entire complex signaling pathway, the invention extracts and targets the critical SMAD phosphorylation step, simplifying the therapeutic mechanism to a focused intervention at this specific molecular node while maintaining high therapeutic effectiveness

Inventive Principle:

Principle #2Taking out (Extraction)

3Reliability

If MYDGF treatment is applied for heart failure, then cardiac function improves, but fibrotic tissue formation increases without intervention

Engineering Contradiction:

Improvecardiac functionVSAvoidfibrotic tissue formation

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent applies the blessing in disguise principle by converting the harmful fibrotic response into a beneficial therapeutic effect. MYDGF treatment transforms the pathological TGF-β1 signaling that normally promotes fibrosis into a protective mechanism by inhibiting SMAD phosphorylation, thereby reducing fibrotic tissue formation while simultaneously improving cardiac function and reducing scar size after myocardial infarction

Inventive Principle:

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

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

MYDGF effectively reduces fibrotic tissue formation, inhibits hypertrophy, and improves heart function by attenuating left ventricular remodeling and enhancing SERCA2a expression, offering a therapeutic approach for various fibrotic and hypertrophic conditions, including chronic heart failure and idiopathic pulmonary fibrosis.

Implementation Method 1

MYDGF protein or its variants, which inhibit transforming growth factor β1-stimulated SMAD phosphorylation and attenuate left ventricular remodeling

Methodology Applied

Scientific EffectSMAD phosphorylation inhibition:

Implementation Method 2

enhancing SERCA2a expression, offering a therapeutic approach for various fibrotic and hypertrophic conditions

Methodology Applied

Scientific EffectSERCA2a expression enhancement:

Data Source

PatentUS20230059560A1Myeloid-derived growth factor for use in treating or preventing fibrosis, hypertrophy or heart failure

Publication Date: 2023.02.23 BOEHRINGER INGELHEIM PHARMA GMBH & CO KG

AI summary

The present invention relates to the protein myeloid-derived growth factor (MYDGF) or nucleic acids encoding said protein for use in treating or preventing fibrosis and hypertrophy. The present invention also relates to the protein MYDGF or nucleic acids encoding said protein for use in treating heart failure. The present invention also relates to vectors comprising the nucleic acid, host cells expressing the nucleic acid, and methods for use in treating fibrosis and hypertrophy, and for use in treating heart failure.