SERCA2a Gene Therapy for DMD Calcium Recycling

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current treatments for Duchenne muscular dystrophy (DMD) face challenges such as immunogenicity concerns with dystrophin expression and the complexity of disease-causing mutations, which limit the effectiveness of gene replacement therapies.

Innovation Solution

Administration of a polynucleotide encoding a sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA)2a polypeptide, specifically using an adeno-associated virus (AAV) vector to deliver the SERCA2a gene to treat skeletal muscular dystrophy, including DMD, by improving calcium recycling and reducing myocardial remodeling and fibrosis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If dystrophin gene replacement therapy is used to treat DMD, then dystrophin expression is restored, but immunogenicity concerns arise and treatment complexity increases

Engineering Contradiction:

Improvedystrophin expression restorationVSAvoidtreatment complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts the essential therapeutic function (calcium homeostasis regulation) from the complex dystrophin gene replacement approach. Instead of attempting to restore the entire dystrophin protein and its multiple functions, the invention isolates and targets the specific calcium pump function (SERCA2a) that is dysfunctional in DMD, thereby simplifying the treatment while maintaining therapeutic efficacy

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent segments the dystrophin protein's functions into distinct components, identifying that calcium pump regulation is a separable and treatable aspect. By focusing specifically on SERCA2a calcium pump function rather than attempting to restore all dystrophin functions simultaneously, the treatment becomes more manageable and less complex

Inventive Principle:

Principle #1Segmentation

2Reliability

If dystrophin gene replacement therapy is used to treat DMD, then dystrophin expression is restored, but immunogenicity concerns arise

Engineering Contradiction:

Improvedystrophin expression restorationVSAvoidimmunogenicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the therapeutic target from the dystrophin protein itself to the SERCA2a calcium pump function. This parameter change shifts the treatment approach from protein replacement to functional restoration, avoiding the immunogenicity issues associated with introducing foreign or repaired dystrophin proteins while still addressing the underlying pathophysiology

Inventive Principle:

Principle #35Parameter changes

3Reliability

If SERCA2a gene therapy is administered, then calcium recycling is improved and myocardial fibrosis is reduced, but long-term durability must be ensured

Engineering Contradiction:

Improvecalcium recycling improvementVSAvoidtreatment durability

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent employs preliminary action by administering the SERCA2a gene therapy before significant myocardial fibrosis and cardiac dysfunction occur. By treating during the intermediate stage when calcium dysregulation is present but before irreversible damage accumulates, the therapy can establish sustained protective effects and maintain durability throughout the disease course

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent ensures continuity of useful action through the use of gene therapy that provides sustained, long-term expression of the SERCA2a protein. The therapeutic effect is not transient but continues indefinitely or for extended periods, maintaining calcium homeostasis regulation and protecting against fibrosis throughout the patient's life

Inventive Principle:

Principle #20Continuity of useful action

Data Source

PatentUS20240058475A1Methods and compositions for treating muscular dystrophy

Publication Date: 2024.02.22 SARDOCOR CORP

AI summary

Some embodiments of the methods and compositions provided herein relate to treating, inhibiting or ameliorating a skeletal muscular dystrophy with a polynucleotide encoding a SERCA2a polypeptide. In some embodiments, the muscular dystrophy comprises Duchenne muscular dystrophy (DMD) or Becker's muscular dystrophy (BMD). In some embodiments, the polynucleotide comprises a viral vector, such as an adeno-associated viral (AAV) vector. More embodiments include methods and compositions to screen for a therapeutic agent to treat, inhibit or ameliorate a skeletal muscular dystrophy in which the screen comprises an in vitro ventricular cardiac tissue model.