Chimp NaV1.8 Sodium Channel Antisense Modulation

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Solution Overview

Problem

Current treatments for chronic pain associated with spinal cord injury are often refractory to standard interventions, and there is a need for effective modulators of sodium channels to manage neuropathic pain without adverse side effects.

Innovation Solution

The development of recombinant nucleic acids and proteins encoding the chimp sodium channel NaV1.8, along with methods for their expression and use in identifying modulators, such as antisense oligonucleotides, to target and inhibit sodium channel activity, facilitating the development of analgesic agents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If standard sodium channel blockers are used to treat neuropathic pain, then pain relief is achieved, but adverse side effects occur due to non-specific blocking of multiple sodium channel isoforms

Engineering Contradiction:

Improvepain management effectivenessVSAvoidadverse side effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention focuses on selectively targeting NaV1.8 sodium channel isoform specifically, rather than blocking all sodium channels. This segmentation approach allows for specific inhibition of the pain-related isoform while preserving other sodium channel functions, thereby achieving pain relief without the adverse side effects associated with non-specific blockers

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent employs compounds with specific molecular structures designed to bind preferentially to NaV1.8 channels. This local quality approach ensures that the pharmacological action is concentrated on the target isoform responsible for neuropathic pain, minimizing off-target effects on other sodium channel isoforms

Inventive Principle:

Principle #3Local quality

2Reliability

If existing sodium channel blockers are used, then some pain relief is achieved, but they lack selectivity for NaV1.8 channels

Engineering Contradiction:

Improvepain reliefVSAvoidselectivity for NaV1.8

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The invention involves developing compounds with specific pharmacological parameters optimized for NaV1.8 selectivity. By adjusting molecular structure parameters and binding affinity characteristics, the patent achieves high selectivity for NaV1.8 channels while maintaining effective pain relief, overcoming the non-specificity of existing blockers

Inventive Principle:

Principle #35Parameter changes

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

This approach potentially provides effective pain management by specifically targeting NaV1.8 channels, reducing neuropathic pain without the deleterious side effects associated with existing treatments.

Implementation Method 1

antisense oligonucleotides, to target and inhibit sodium channel activity

Methodology Applied

Scientific EffectComplementary base pairing:

Implementation Method 2

TTX is a toxin that blocks the conduction of nerve impulses along the axons and leads to paralysis. It binds to sodium channels and blocks the flow of sodium ions.

Methodology Applied

Scientific EffectToxin binding:

Data Source

PatentUS7972813B2Tetrodotoxin-resistant sodium channel alpha subunit

Publication Date: 2011.07.05 VERTEX PHARMACEUTICALS INC

AI summary

The present invention is directed to a chimp sodium channel alpha subunit and methods and compositions for making and using the same.