Small Molecules Up-regulating Voltage-gated Sodium Channel Alpha Subunits

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Solution Overview

Problem

Current methods for modulating protein expression, such as gene therapy and antisense technology, primarily focus on down-regulating protein levels, with limited approaches for up-regulating specific genes like the SCNA gene family associated with voltage-gated sodium channels, which are crucial for treating various diseases.

Innovation Solution

The use of small molecules like milnacipran, torsemide, risperidone, pinacidil, benidipine, ketoconazole, ebselen, tadalafil, zeranol, nefazadone, lomerizine, icariin, omeprazole, L-694,247, nitrendipine, nimetazepam, amlexanox, mosapride, sertraline, or stanozolol to modulate the expression and function of alpha subunits of voltage-gated sodium channels, either by up-regulating mRNA levels or interfering with RNA functions to enhance protein production.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If antisense technology or siRNA is used to modulate protein expression, then down-regulation of protein levels is achieved, but up-regulation of specific genes like SCNA is not possible

Engineering Contradiction:

Improveability to up-regulate genesVSAvoidlimitation of existing approaches

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

Instead of using antisense technology to down-regulate proteins, the patent applies the inverse approach by using small molecules to up-regulate SCNA gene expression and protein levels, thereby treating sodium channel dysfunction through increased rather than decreased expression

Inventive Principle:

Principle #13The other way round (Inversion)

2Quantity of substance

If gene therapy or antisense technology is used, then protein expression can be modulated, but the approach is complex and has limited applicability to up-regulating specific genes

Engineering Contradiction:

Improveprotein expression levelVSAvoidcomplexity of gene therapy and antisense technology

Core Design Contradiction:

Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent replaces complex gene therapy and antisense technology with small molecule compounds that can modulate SCNA expression through simpler biochemical mechanisms, thereby achieving protein expression modulation without the complexity of nucleic acid-based therapies

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Quantity of substance

If small molecules are used to modulate SCNA expression, then up-regulation of mRNA and protein levels is achieved, but the mechanism of action is not fully understood

Engineering Contradiction:

ImprovemRNA and protein levelsVSAvoidmechanism of action

Core Design Contradiction:

Quantity of substanceVSDifficulty of detecting and measuring

Solution Approach 1:

The patent uses small molecules as intermediaries to modulate SCNA expression, where these compounds act as mediators between the cellular environment and the SCNA gene expression machinery, enabling up-regulation without requiring direct manipulation of the gene itself

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS10583128B2Treatment of diseases related to alpha subunits of sodium channels, voltage-gated (SCNxA) with small molecules

Publication Date: 2020.03.10 CURNA INC

AI summary

Small compounds that modulate the expression of and/or function of sodium channel, voltage-gated, alpha subunit (SCNxA) are presented. Pharmaceutical compositions containing such small molecules and their use in treating diseases and disorders associated with the expression of SCNxA are also presented.