Antisense Oligonucleotides Target Dynamin 2 for Neuropathy Treatment

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current therapeutic options are inadequate for effectively treating centronuclear myopathies (CNM) and Charcot-Marie-Tooth disease (CMT), particularly due to the lack of effective methods to reduce dynamin 2 protein levels, which are detrimental to muscle and nerve tissues.

Innovation Solution

Development of antisense oligonucleotides (AONs) that specifically target and reduce the expression of dynamin 2 by interfering with its splicing or translation, thereby decreasing its protein levels in muscles and nerves.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If dynamin 2 expression is reduced using AONs, then muscle and nerve tissue function is improved, but the complexity of the therapeutic approach increases

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidtreatment complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

Antisense oligonucleotides (AONs) are introduced as intermediary molecules that bind to dynamin 2 mRNA to inhibit its translation into protein. This mediator approach allows selective reduction of dynamin 2 expression without directly modifying the gene or using complex gene editing tools, thereby improving therapeutic effectiveness while maintaining relative simplicity in the treatment mechanism.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Quantity of substance

If AONs are used to target dynamin 2, then protein levels are reduced, but the manufacturing and delivery complexity increases

Engineering Contradiction:

Improvedynamin 2 protein levelsVSAvoidAON production and delivery

Core Design Contradiction:

Quantity of substanceVSEase of manufacture

Solution Approach 1:

The patent employs antisense oligonucleotides as disposable, short-lived therapeutic agents that can be synthesized chemically and administered systemically. These AONs are designed to be transient rather than permanent, allowing for repeated dosing if needed, and can be produced through established oligonucleotide synthesis methods without requiring complex manufacturing infrastructure or long-term storage facilities.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

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

The AONs demonstrate promise by reducing dynamin 2 production and improving molecular, histological, physical, and functional characteristics of muscles, offering a potential therapeutic approach for CNM and CMT patients by normalizing dynamin 2 expression levels.

Implementation Method 1

antisense oligonucleotides (AON) which target the dynamin 2 gene and their use for the treatment of centronuclear myopathies (CNM), particularly myotubular myopathy (XLMTM), and Charcot-Marie-Tooth disease (CMT)

Methodology Applied

Scientific EffectAntisense hybridization: Absorption (EM radiation)

Data Source

PatentUS11499154B2Antisense targeting dynamin 2 and use for the treatment of centronuclear myopathies and neuropathies

Publication Date: 2022.11.15 GENETHON

AI summary

The present invention concerns the use of antisense oligonucleotides (AON) capable of inhibiting expression of dynamin 2, advantageously human dynamin 2, for use in the treatment of Charcot-Marie-Tooth disease (CMT) and centronuclear myopathies (CNM).