Stage-Specific WNT Modulation for Retinal Neovascularization

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Existing treatments for retinopathies, such as diabetic retinopathy and familial exudative vitreoretinopathy, fail to effectively modulate WNT signaling to address aberrant vascular development and neovascularization, leading to retinal ischemia, hemorrhage, and vision loss.

Innovation Solution

Administration of engineered WNT signaling modulators, including agonists and antagonists, that bind to Fzd, LRP, or Tspan12 receptors, optionally combined with VEGF or Ang2 antagonists, to regulate vascular formation at different stages of retinopathy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If WNT signaling is activated to promote vascular development, then retinal vascularization is improved, but aberrant neovascularization and vascular damage occur

Engineering Contradiction:

Improveretinal vascularizationVSAvoidaberrant neovascularization

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent applies dynamics by transitioning from static WNT signaling activation to dynamic, stage-specific modulation. WNT agonists are administered in early stages to promote vascularization, while WNT antagonists are administered in late stages to suppress aberrant neovascularization. This temporal differentiation of signaling modulation resolves the contradiction between promoting vascular development and preventing harmful neovascularization.

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The treatment protocol segments the WNT signaling modulation into distinct phases: early retinopathy stage (pro-vascularization with WNT agonists) and late retinopathy stage (anti-neovascularization with WNT antagonists). This segmentation allows targeted intervention at different disease stages, simultaneously achieving vascularization promotion and aberrant growth suppression.

Inventive Principle:

Principle #1Segmentation

2Reliability

If WNT agonists are used to treat early retinopathy, then vascular development is promoted, but treatment complexity increases

Engineering Contradiction:

Improvevascular developmentVSAvoidtreatment protocol

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The treatment protocol is segmented into two distinct phases based on disease stage: early retinopathy treatment with WNT agonists and late retinopathy treatment with WNT antagonists. Each phase has specific indications and treatment objectives, which simplifies the overall treatment strategy by providing clear stage-specific guidance rather than a single complex universal protocol.

Inventive Principle:

Principle #1Segmentation

3Object-generated harmful factors

If WNT antagonists are used to suppress neovascularization, then aberrant vascular growth is reduced, but retinal ischemia worsens

Engineering Contradiction:

ImproveneovascularizationVSAvoidretinal ischemia

Core Design Contradiction:

Object-generated harmful factorsVSObject-affected harmful factors

Solution Approach 1:

The patent applies dynamics by implementing stage-specific WNT signaling modulation: WNT agonists are used in early stages when vascularization is deficient, while WNT antagonists are used in late stages when aberrant neovascularization is the primary problem. This temporal differentiation ensures that ischemia is not exacerbated by antagonist treatment, as it is administered only after adequate vascularization has occurred.

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

WNT agonist treatment is administered as a preliminary action in early retinopathy stages to establish adequate retinal vascularization before WNT antagonist treatment begins in late stages. This preliminary vascularization ensures that the retina has sufficient blood supply before suppressing neovascularization, preventing the exacerbation of retinal ischemia.

Inventive Principle:

Principle #10Preliminary action

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

Regulating WNT signaling through agonists and antagonists helps control aberrant vascular growth, reducing neovascularization and associated retinal damage, potentially improving treatment outcomes for retinopathies like diabetic retinopathy and FEVR.

Implementation Method 1

WNT signaling has been implicated as an important pathway for the vascular development in retina. Growing genetic evidences from human and rodent studies further support the importance of WNT signaling in retinal vasculature

Methodology Applied

Scientific EffectSignal transduction:

Implementation Method 2

Norrin, WNT signal ligand, transmits a signal to the endothelial cells through a receptor complex composed of Fzd4/Lrp5/Tspan12 for normal retinal vascularization in eye

Methodology Applied

Scientific EffectLigand-receptor binding:

Implementation Method 3

The ischemic condition induces the production of vascular endothelial growth factor (VEGF) and angiopoietin2 (Ang2), leading to neovascularization and vascular tuft formation

Methodology Applied

Scientific EffectIschemia-induced factor production:

Data Source

PatentUS20250313616A1Modulation of WNT signalling in ocular disorders

Publication Date: 2025.10.09 SURROZEN OPERATING INC

AI summary

The present invention provides methods of treating ocular disorders with modulators of the WNT signaling pathway. In particular the ocular disorders are retinopathies. Also provided are methods of dosing and pharmaceutical compositions.