PTPσ Inhibition for Root Avulsion Injury Repair

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Solution Overview

Problem

Root avulsion injuries, which physically separate spinal nerves from the spinal cord, result in severe disruption, neuron death, and muscle atrophy due to inhibitory chondroitin sulfate proteoglycans (CSPGs) in the scar tissue, hindering axon regeneration and motor function recovery.

Innovation Solution

Administration of a therapeutic agent that inhibits the catalytic activity or signaling of PTPσ, such as a therapeutic peptide with a sequence homologous to the wedge domain of PTPσ, to promote motoneuron survival, axon regeneration, and motor function recovery by facilitating axon growth across inhibitory central nervous system scars.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If surgical reimplantation is performed to restore motor function, then motoneuron survival and axonal regeneration can occur, but axon regeneration and functional recovery remain unsatisfactory due to inhibitory CSPGs in scar tissue

Engineering Contradiction:

Improvemotor function recoveryVSAvoidCSPG inhibition

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent converts the harmful effect of CSPGs into a beneficial one by using Chondroitinase ABC (ChABC) enzyme to digest and break down CSPGs in the scar tissue. This enzymatic degradation transforms the inhibitory environment into a permissive one, enabling axon regeneration and improving functional recovery after root avulsion injury

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent introduces Chondroitinase ABC (ChABC) as an intermediary substance that mediates between the inhibitory CSPGs and the regenerating axons. The enzyme acts as a biochemical mediator that selectively degrades CSPGs, removing the inhibitory barrier and facilitating axon growth through the scar tissue without directly affecting the axons themselves

Inventive Principle:

Principle #24Intermediary (Mediator)

2Ease of operation

If astrocytes form channels in basal lamina to allow motor fibers passage, then nerve regeneration is facilitated, but after avulsion injury astrocytes rearrange and hypertrophy to form TZ scar that impedes growth

Engineering Contradiction:

Improveaxon passage through TZVSAvoidastrocyte structure

Core Design Contradiction:

Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent converts the harmful hypertrophied astrocyte scar formation into a beneficial outcome by using ChABC to digest the CSPGs that these astrocytes produce. The same astrocytes that create the inhibitory environment are targeted indirectly through their CSPG product, transforming their harmful output into an opportunity for therapeutic intervention

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent changes the biochemical parameters of the scar tissue environment by introducing ChABC enzyme that specifically degrades CSPGs. This alters the chemical composition and physical properties of the extracellular matrix, transforming it from an inhibitory state to a permissive state for axon regeneration

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS10898550B2Compositions and methods of treating root avulsion injury

Publication Date: 2021.01.26 VERSITECH LTD

AI summary

A method of treating root avulsion injury in a subject in need thereof includes administering to the subject a therapeutic agent that inhibits one or more of catalytic activity, signaling, and function of PTPσ.