cAMP Modulation for Astroglial Edema Reduction

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Solution Overview

Problem

Current treatments for astroglial edema and related neurological conditions such as multiple sclerosis, Alzheimer's disease, and epilepsy lack effective mechanisms to reduce astrocytic cytoplasmic excitability and cell swelling, which are central to the pathophysiology of these disorders.

Innovation Solution

Elevating cAMP levels in astrocytes using β-adrenergic receptor agonists, lactate receptor agonists, or phosphodiesterase inhibitors to reduce astroglial edema by modulating cytoplasmic excitability and glucose metabolism, thereby addressing the underlying pathophysiological mechanisms.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional treatments are used for astroglial edema, then current standard therapies are applied, but they lack effective mechanisms to reduce astrocytic cytoplasmic excitability and cell swelling

Engineering Contradiction:

Improveeffectiveness of treatmentVSAvoidmechanism coverage

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies parameter changes by modulating intracellular cAMP levels through multiple pathways (β-adrenergic receptor agonists, lactate receptor agonists, phosphodiesterase inhibitors) to treat astroglial edema. This changes the biochemical parameter (cAMP concentration) to achieve therapeutic effect where conventional treatments fail.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces cAMP as an intermediary molecule that mediates the effect of various agonists and inhibitors on astrocyte function. By targeting cAMP signaling pathways, the treatment indirectly regulates cytoplasmic excitability and cell volume, providing a versatile mechanism that addresses multiple aspects of astroglial edema.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If cAMP levels are elevated in astrocytes to reduce edema, then astroglial edema and cytoplasmic excitability are reduced, but this requires specific receptor targeting and signaling modulation

Engineering Contradiction:

Improveastroglial edemaVSAvoidsignaling pathway modulation

Core Design Contradiction:

Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent segments the complex cAMP signaling system into distinct targetable components: β-adrenergic receptors, lactate receptors (GPR81), and phosphodiesterase enzymes. This segmentation allows selective pharmacological intervention at different points in the signaling pathway, reducing edema through multiple discrete mechanisms rather than requiring modulation of the entire system.

Inventive Principle:

Principle #1Segmentation

3Ease of operation

If β-adrenergic receptor agonists are used to elevate cAMP, then cytoplasmic excitability is attenuated, but specific receptor types must be targeted

Engineering Contradiction:

Improvecytoplasmic excitability controlVSAvoidreceptor specificity

Core Design Contradiction:

Ease of operationVSAdaptability or versatility

Solution Approach 1:

The patent employs multiple agonists that can target different receptor types (β-adrenergic receptors, lactate receptors) to achieve the same therapeutic effect of elevating cAMP and reducing cytoplasmic excitability. This multi-functionality provides versatility in treatment approaches while maintaining ease of operation through various pharmacological options.

Inventive Principle:

Principle #6Universality (Multi-functionality)

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 approach effectively reduces astroglial edema and attenuates cytoplasmic excitability, providing a neuroprotective mechanism that can treat conditions like multiple sclerosis, Alzheimer's disease, and epilepsy by increasing cAMP levels, thereby improving cellular and synaptic functions.

Implementation Method 1

The activation of β-AR/cAMP signaling pathway in astrocytes by the 'fight or flight response' neurotransmitter/hormone noradrenaline/adrenaline (NA/ADR), respectively, has been shown to promote rapid degradation of glycogen in astrocytes

Methodology Applied

Scientific EffectcAMP signaling pathway activation:

Implementation Method 2

an agent elevating the cAMP level in astrocytes for use in reducing astroglial edema, wherein the agent is an agonist for a β-adrenergic receptor (β-AR), an agonist for a lactate receptor or a phosphodiesterase (PDE) inhibitor

Methodology Applied

Scientific EffectPhosphodiesterase inhibition:

Implementation Method 3

the results in this study show that GPR81 is present in astrocytes and that the activation of this receptor by lactate or 3-Chloro-5-hydroxybenzoic acid (3-Cl-5-HBA), an agonist of this receptor, elevates cytosolic cAMP

Methodology Applied

Scientific EffectGPR81 receptor activation:

Data Source

PatentEP3013352B1Mechanism and drug targets for reducing cell edema (neuroprotection) and cytoplasmic excitability in astrocytes in normal and pathological states

Publication Date: 2018.09.05 CELICA BIOMEDICAL

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AI summary

The present invention pertains to a method for screening a compound useful in reducing astroglial edema, said method comprising: (i) providing a compound; (ii) bringing said compound in contact with an astrocyte; and (iii) determining the cAMP level in said astrocyte contacted with said compound; wherein said compound is identified as a compound useful in reducing astroglial edema, if the cAMP level in the astocyte increases after contact. The present invention further pertains to an agent elevating the cAMP level in astrocytes for use in reducing astroglial edema.