BAG3 Gene Therapy for Variant-Specific Dilated Cardiomyopathy

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Solution Overview

Problem

There is a higher incidence and prevalence of non-ischemic or ischemic dilated cardiomyopathy (DCM) in individuals of African ancestry, attributed to specific BAG3 genetic variants, leading to increased risk of death or heart failure hospitalization.

Innovation Solution

Administering a therapeutically effective amount of an agent that modulates the expression or amount of BAG3 molecules, proteins, or peptides in target cells or tissues, specifically targeting in-frame insertions or other genetic variants of the BAG3 gene, such as p.Ala160dup, to normalize BAG3 function.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If BAG3 gene therapy is administered to patients with cardiac disease, then BAG3 expression is modulated to improve cardiac outcomes, but the presence of specific genetic variants (such as p.Ala160dup) in individuals of African ancestry may negatively influence treatment effectiveness

Engineering Contradiction:

Improvecardiac outcomesVSAvoidtreatment effectiveness across different genetic backgrounds

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies local quality by identifying specific genetic variants (such as p.Ala160dup) in the BAG3 gene that are prevalent in individuals of African ancestry and negatively influence treatment response. The therapy is tailored to account for these localized genetic differences, ensuring that treatment effectiveness is optimized for specific patient populations based on their genetic background.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent employs parameter changes by modulating BAG3 expression levels through gene therapy to compensate for the negative effects of specific genetic variants. By adjusting the expression parameters of the BAG3 gene, the therapy aims to normalize protein function and improve cardiac outcomes despite the presence of detrimental genetic variations.

Inventive Principle:

Principle #35Parameter changes

2Strength

If BAG3 expression is increased through gene therapy, then cardiac function may be improved, but the presence of in-frame insertions may lead to abnormal protein function or aggregation

Engineering Contradiction:

Improvecardiac functionVSAvoidprotein function

Core Design Contradiction:

StrengthVSStability of the object's composition

Solution Approach 1:

The patent applies preliminary action by first identifying and characterizing specific genetic variants (such as in-frame insertions) before administering BAG3 gene therapy. This preliminary genetic screening allows clinicians to predict which patients may benefit from increased BAG3 expression and which patients may experience adverse effects, enabling proactive treatment planning and risk mitigation.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent employs feedback mechanisms by monitoring BAG3 expression levels and cardiac function responses in patients receiving gene therapy. This feedback allows for adjustment of treatment parameters and identification of patients whose genetic background may be causing adverse effects, enabling real-time optimization of therapy effectiveness and safety.

Inventive Principle:

Principle #23Feedback

Data Source

PatentUS12516376B2Optimizing BAG3 gene therapy

Publication Date: 2026.01.06 TEMPLE UNIV

AI summary

Identification of BAG3 (Bcl2-associated anthanogene 3) genetic variants were associated with the prevalence non-ischemic or ischemic dilated cardiomyopathy (DCM) and DCM outcomes in individuals of African ancestry.