AAV2/9 CASQ2 Gene Transfer for Recessive CPVT Arrhythmia

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Recessive Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is characterized by severe arrhythmias triggered by emotional stress or mild exercise, with incomplete therapeutic responses and complex cellular pathophysiology, particularly due to mutations in the CASQ2 gene leading to functional derangements in cardiac cells.

Innovation Solution

Delivering the CASQ2 gene into cardiac cells via viral gene transfer using the AAV2/9 vector to restore physiological levels of CASQ2 protein and its associated proteins, thereby correcting ultrastructural and functional abnormalities.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If viral gene transfer is used to restore CASQ2 in cardiac cells, then the functional derangements and arrhythmias are corrected, but the complexity of the treatment method increases

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidtreatment method complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent uses an adeno-associated virus (AAV) vector as an intermediary carrier to deliver the CASQ2 gene into cardiac cells. The AAV vector serves as a mediator that protects the genetic material during delivery and enables efficient transduction of cardiac tissue, thereby achieving effective gene transfer while simplifying the overall treatment approach compared to direct gene injection methods.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Ease of operation

If conventional therapies are used for recessive CPVT, then treatment is provided, but the therapeutic response is incomplete due to complex cellular pathophysiology

Engineering Contradiction:

Improvetreatment accessibilityVSAvoidtherapeutic response completeness

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent extracts and addresses the root cause of recessive CPVT by directly delivering the functional CASQ2 gene into cardiac cells. This approach bypasses conventional symptomatic treatments and directly targets the underlying genetic defect, thereby achieving complete therapeutic response by removing the fundamental pathological element rather than managing symptoms.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent performs preliminary restoration of CASQ2 protein function before arrhythmias can occur or worsen. By proactively delivering the functional gene and restoring protein expression in advance, the treatment prevents the development of functional derangements and arrhythmias rather than treating them after they manifest, thereby achieving complete therapeutic response.

Inventive Principle:

Principle #10Preliminary action

3Reliability

If CASQ2 mutations are present, then recessive CPVT develops with severe arrhythmias, but the ultrastructural and functional abnormalities in cardiac cells persist

Engineering Contradiction:

Improvearrhythmia suppressionVSAvoidcellular ultrastructure stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent changes the genetic parameter by introducing a functional CASQ2 gene into cardiac cells with mutant or absent CASQ2. This genetic parameter change leads to restoration of CASQ2 protein expression, which subsequently restores the ultrastructural organization and functional properties of cardiac cells, thereby stabilizing cellular composition and suppressing arrhythmias simultaneously.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS11173215B2Method of gene transfer for the treatment of recessive catecholaminergic polymorphic ventricular tachycardia (CPVT)

Publication Date: 2021.11.16 INSTI CLINICI SCII MAUGERI S P A SB

AI summary

The present invention concerns a method for the treatment of recessive Catecholaminergic Polymorphic Ventricular Tachycardia comprising delivering a gene into a cardiac cell.