BMP6 Signaling for Targeted Melanin Transfer Modulation

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Solution Overview

Problem

Current understanding of melanin transfer from melanocytes to keratinocytes is limited, which is crucial for controlling skin and hair pigmentation, and existing methods for modulating melanin pigmentation often have adverse effects or target melanogenesis rather than the transfer process.

Innovation Solution

The use of BMP6 or its variants to stimulate melanin transfer from melanocytes to keratinocytes, along with BMP6 antagonists like sclerostin, chordin-like, or follistatin-related protein, to modulate melanin pigmentation by influencing the expression and activity of key receptors and proteins involved in melanin transfer.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing methods target melanogenesis to modulate pigmentation, then pigmentation can be modulated, but adverse effects occur

Engineering Contradiction:
Improvesafety of pigmentation modulationVSAvoidadverse effects
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention extracts and targets specifically the melanin transfer process from melanocytes to keratinocytes, separating this function from melanogenesis. By using BMP6 antagonists to inhibit only the transfer step rather than affecting melanin synthesis, the method achieves pigmentation modulation without the adverse effects associated with targeting melanogenesis

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention introduces BMP6 and its antagonists as intermediary molecules that specifically regulate the melanin transfer process. These intermediaries bind to BMP receptors on keratinocytes to control melanosome transfer, providing a targeted mechanism that avoids the broad effects and adverse reactions caused by direct melanogenesis inhibition

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of manufacture

If melanin transfer process is not well understood, then targeted modulation is difficult, but knowledge gap limits effective treatment development

Engineering Contradiction:
Improveease of developing targeted treatmentVSAvoidknowledge gap in melanin transfer
Core Design Contradiction:
Ease of manufactureVSLoss of information

Solution Approach 1:

The invention performs preliminary action by identifying and characterizing the BMP6-BMP receptor interaction pathway that controls melanin transfer before developing therapeutic applications. This preliminary research establishes the molecular mechanism and validates the target, making subsequent targeted treatment development straightforward and effective

Inventive Principle:
Principle #10Preliminary action

3Productivity

If BMP6 is used to stimulate melanin transfer, then melanin transfer increases, but specificity of targeting must be maintained

Engineering Contradiction:
Improvemelanin transfer efficiencyVSAvoidtargeting specificity
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The invention applies local quality by using BMP6 antagonists that specifically bind to BMP receptors located on keratinocyte surfaces. This localized targeting ensures that only the melanin transfer function is affected, while maintaining high productivity through direct action at the transfer site without off-target effects

Inventive Principle:
Principle #3Local quality

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 allows for targeted modulation of skin and hair pigmentation, reducing adverse effects and enhancing melanin transfer, thereby providing a more effective method for cosmetic and therapeutic applications, including skin lightening, darkening, and treating conditions like hyperpigmentation and hypopigmentation.

Implementation Method 1

BMP signalling operates at multiple levels depending on BMP type, presence of antagonist(s), development stage of target tissue, and target cell receptor type. BMPs bind two transmembrane receptor families, multiple BMP receptor (BMPR)I and a single BMPRII. Interestingly, to initiate signalling, BMP has to bind both receptors, inducing phosphorylation of an intracellular domain in BMPRI by BMP-RII and activating intracellular signal transduction.

Methodology Applied
Scientific EffectSignal transduction:

Implementation Method 2

The invention also provides use of a composition comprising the BMP6 antagonist sclerostin, chordin-like or follistatin-related protein (FSRP) for reducing melanin pigmentation of the skin and/or hair of a subject

Methodology Applied
Scientific EffectAntagonist binding:

Data Source

PatentEP2331057B1Compositions and methods for modulating skin pigmentation
Publication Date: 2019.03.20 UNIVERSITY OF BRADFORD
  • EP2331057B1 patent drawingFigure 1A~1B
  • EP2331057B1 patent drawingFigure 2A~2B
  • EP2331057B1 patent drawingFigure 3A~3B

AI summary

The present invention relates to compositions and methods useful in studying or modulating melanin pigmentation in the skin. Particularly, the invention relates to compositions comprising a substance capable of modulating the activity or expression of ALK6 (SEQ ID 2) or Cdc42 which in turn are capable of modulation of the transfer of melanin from melanocytes to keratinocytes and potentially from keratinocytes to keratinocytes. The invention also relates to assays for identifying such compositions, and methods of modulating skin pigmentation.