S1P Receptor Modulators Induce BDNF Production

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Solution Overview

Problem

Current treatments for neurodegenerative diseases and peripheral nervous system disorders, such as Rett syndrome, do not effectively address the underlying neuronal survival and differentiation issues, particularly in inducing brain-derived neurotrophic factor (BDNF) production.

Innovation Solution

S1P receptor modulators, specifically sphingosine analogues like 2-substituted 2-amino-propane-1,3-diol derivatives, which act as agonists to increase BDNF production by signaling through sphingosine-1-phosphate receptors, thereby treating or preventing conditions associated with BDNF levels.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional treatments for neurodegenerative diseases are used, then current standard therapy is maintained, but neuronal survival and differentiation issues are not effectively addressed

Engineering Contradiction:

Improveeffectiveness in addressing neuronal survival and differentiationVSAvoidability to induce BDNF production

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent changes the pharmacological parameter by using S1P receptor modulators instead of conventional treatments. These modulators bind to sphingosine-1-phosphate receptors and alter signaling pathways to specifically induce BDNF production, thereby improving neuronal survival and differentiation effectiveness.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces BDNF as an intermediary substance that mediates neuronal survival and differentiation. S1P receptor modulators act as intermediaries to stimulate BDNF production, which then exerts protective effects on neurons, solving the problem of ineffective conventional treatments.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If S1P receptor modulators are used to induce BDNF production, then neuronal survival and differentiation are improved, but the mechanism complexity increases

Engineering Contradiction:

Improveneuronal survival and differentiationVSAvoidsignaling pathway complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts the essential function from complex neuroprotective processes and identifies BDNF production as the key mechanism. By focusing on S1P receptor modulation that specifically induces BDNF, the patent simplifies the approach while maintaining effectiveness in neuronal survival and differentiation.

Inventive Principle:

Principle #2Taking out (Extraction)

3Reliability

If BDNF production is induced by S1P receptor modulators, then treatment efficacy for neurodegenerative diseases is improved, but potential side effects increase

Engineering Contradiction:

Improvetreatment efficacyVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by targeting specific S1P receptors (particularly S1P1) that are selectively expressed in certain tissue locations. This selective binding induces BDNF production in relevant neural tissues while minimizing off-target effects, thereby improving treatment efficacy while controlling side 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

The S1P receptor modulators effectively induce BDNF production, delaying or preventing the progression of neurodegenerative diseases and peripheral nervous system disorders by stimulating BDNF expression, as demonstrated in animal and clinical trials, showing therapeutic potential for conditions like Rett syndrome.

Implementation Method 1

Agonist binding to a S1P receptor may e.g. result in dissociation of intracellular heterotrimeric G-proteins into Gα-GTP and Gβγ-GTP

Methodology Applied

Scientific EffectG-protein dissociation:

Implementation Method 2

increased phosphorylation of the agonist-occupied receptor and activation of downstream signaling pathways/kinases

Methodology Applied

Scientific EffectPhosphorylation:

Implementation Method 3

S1P receptor modulators can induce BDNF production... by inducing BDNF production (or stimulating BDNF expression)

Methodology Applied

Scientific EffectTranscriptional activation:

Data Source

PatentEP2142184B1Use of s1p receptor modulator

Publication Date: 2018.10.24 NOVARTIS AG

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Figure 3A~3C

AI summary

Use of an S1P receptor modulator in the treatment or prevention of a disease or condition dependent on brain-derived neurotrophic factor (BDNF) expression.