AAV9 Vector Delivery for Cardiac and Skeletal Dysfunction in MPS

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Solution Overview

Problem

Current treatments for mucopolysaccharidoses, such as enzyme replacement therapy and hematopoietic stem cell transplantation, do not effectively address cardiac and skeletal manifestations, which are major causes of death in patients with lysosomal storage diseases.

Innovation Solution

Administration of a recombinant AAV9 vector encoding alpha-L-iduronidase or other lysosomal enzymes via intravenous or intrathecal routes to achieve high enzyme activity in major organs, preventing cardiac and skeletal dysfunction in mammals with mucopolysaccharidosis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If enzyme replacement therapy (ERT) or hematopoietic stem cell transplantation (HSCT) is used, then peripheral metabolic storage disease symptoms are alleviated, but cardiac and skeletal manifestations are not remedied

Engineering Contradiction:

Improveeffectiveness of therapyVSAvoidcoverage of disease manifestations

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent segments the delivery approach by using different administration routes (intravenous for cardiac/skeletal targets, intrathecally for CNS targets) to address different disease manifestations separately, allowing each route to optimize for its specific target organs

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent uses AAV9 vectors as intermediaries to deliver functional enzyme genes to target cells, bridging the gap between systemic enzyme replacement and tissue-specific gene expression to achieve sustained therapeutic enzyme production in cardiac and skeletal tissues

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If AAV-mediated gene therapy is administered to achieve high enzyme activity in major organs, then cardiac and skeletal dysfunction is prevented, but complex vector administration protocols are required

Engineering Contradiction:

Improveenzyme activity levelVSAvoidadministration protocol complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs dynamic, adaptive administration protocols that adjust vector dosage and routing based on disease severity and patient response, allowing optimization of enzyme activity levels while managing protocol complexity through personalized treatment strategies

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The AAV9 vector system serves multiple functions simultaneously: it delivers therapeutic enzymes to cardiac tissue, skeletal tissue, and CNS structures through a single platform that can be administered via different routes depending on the primary disease manifestation

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20240316217A1Methods for preventing cardiac or skeletal defects in diseases including mucopolysaccharidoses

Publication Date: 2024.09.26 REGENXBIO RS LLC

AI summary

A method to prevent, inhibit the progression of, reduce the severity of, or treat cardiac, vascular or skeletal dysfunction or defect(s) in a human having lysosomal storage disorder, is provided.