Peptides Modulating Nav1.8 Trafficking via Magi-1 Targeting

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Solution Overview

Problem

There is a continuing need for development of agents that act on Nav1.8 channels to increase or decrease a subject's pain sensitivity, as the precise molecular mechanisms controlling Nav1.8 channel trafficking are not completely understood.

Innovation Solution

The use of peptides, compositions, and methods involving Magi-1 targeting shRNA or siRNA to treat pain, induce analgesia, or increase pain sensitivity by targeting Nav1.8 channels.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If Nav1.8 channel blockers are used for pain relief, then pain sensitivity is decreased, but the mechanism is not fully understood and specific agents remain elusive

Engineering Contradiction:

Improvepain sensitivityVSAvoidmolecular mechanism understanding

Core Design Contradiction:

Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent introduces Magi-1 as an intermediary protein that mediates the trafficking and membrane localization of Nav1.8 channels. By targeting Magi-1 with peptides or siRNA, the invention provides a specific molecular agent that indirectly modulates Nav1.8 channel function, resolving the difficulty of finding direct Nav1.8 blockers while achieving pain relief through controlled channel trafficking

Inventive Principle:

Principle #24Intermediary (Mediator)

2Adaptability or versatility

If Nav1.8 channel trafficking is perturbed to affect channel functioning, then pain sensitivity can be modulated, but the precise molecular mechanisms are not completely understood

Engineering Contradiction:

Improvepain sensitivity modulationVSAvoidmolecular mechanism knowledge

Core Design Contradiction:

Adaptability or versatilityVSLoss of information

Solution Approach 1:

The patent identifies and targets Magi-1, a protein that precedes and controls Nav1.8 channel trafficking to the membrane. By interfering with Magi-1 function using siRNA or peptides before Nav1.8 channels reach the membrane, the invention modulates pain sensitivity while providing insight into the molecular mechanism of channel trafficking that was previously unknown

Inventive Principle:

Principle #10Preliminary action

3Object-generated harmful factors

If peptides or Magi-1 targeting siRNA are used to treat pain, then narcotics can be replaced, but the complexity of delivery and administration increases

Engineering Contradiction:

Improvenarcotic dependencyVSAvoidadministration complexity

Core Design Contradiction:

Object-generated harmful factorsVSEase of operation

Solution Approach 1:

The patent replaces narcotic-based pain management with a molecular biology approach using siRNA or peptides that target Magi-1. This substitution eliminates narcotic dependency by using RNA interference or peptide-mediated disruption of the Magi-1/Nav1.8 interaction, providing a non-narcotic alternative for pain treatment

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Data Source

PatentUS20250154199A1Peptides for treating pain or reducing pain sensitivity

Publication Date: 2025.05.15 THE RES FOUNDATION FOR THE STATE UNIV OF NEW YORK

AI summary

Described herein are peptides that can be used to treat pain or increase pain sensitivity in subject in need of treatment. Additionally, peptides of the present disclosure can be administered with an analgesic agent and/or anesthetic agent. Peptides of the present disclosure are suitable for use when a subject in need of treatment has an injury, a chronic disease, a chronic inflammation, Morton's neuroma, operative/post-operative pain, or a combination thereof.