BACE1 Inhibitor and mGluR Agonist Combination for Alzheimer's

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Solution Overview

Problem

Current BACE1 inhibitors for treating Alzheimer's disease fail to improve cognitive functions despite reducing amyloid deposition, likely due to their impact on synaptic function, leading to undesirable side effects.

Innovation Solution

Combining BACE1 inhibitors with metabotropic glutamate receptor (mGluR) agonists, specifically mGluR1 positive allosteric modulators, to counteract BACE1-mediated synaptic deficits and enhance synaptic plasticity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If BACE1 inhibitors are used to reduce amyloid deposition, then amyloid plaque formation is reduced, but cognitive function deteriorates due to synaptic impairment

Engineering Contradiction:

Improveamyloid depositionVSAvoidcognitive function

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent introduces mGluR agonists as intermediary substances that mediate between BACE1 inhibition and cognitive function preservation. These agonists activate metabotropic glutamate receptors to compensate for synaptic deficits caused by BACE1 inhibition, thereby maintaining cognitive function while allowing amyloid reduction to proceed

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the pharmacological parameters by combining BACE1 inhibitors with mGluR agonists. This combination modifies the net effect on synaptic transmission and cognitive function, allowing the system to achieve both amyloid reduction and cognitive function maintenance through altered receptor activation patterns

Inventive Principle:

Principle #35Parameter changes

2Quantity of substance

If BACE1 inhibitors are administered to treat Alzheimer's disease, then amyloid production is reduced, but synaptic plasticity is impaired

Engineering Contradiction:

Improveamyloid productionVSAvoidsynaptic plasticity

Core Design Contradiction:

Quantity of substanceVSStability of the object's composition

Solution Approach 1:

mGluR agonists serve as intermediary agents that restore synaptic plasticity mechanisms affected by BACE1 inhibition. By activating metabotropic glutamate receptors, these agonists compensate for the synaptic deficits and maintain long-term potentiation, thereby preserving synaptic plasticity while allowing continued amyloid production reduction

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates a composite therapeutic approach by combining BACE1 inhibitors with mGluR agonists. This composite treatment strategy addresses both amyloid pathology and synaptic plasticity deficits simultaneously, achieving a more comprehensive treatment effect than either drug alone

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS12156879B2Combining BACE1 inhibitors with mGluR agonists for Alzheimer's disease therapy

Publication Date: 2024.12.03 UNIV OF CONNECTICUT

AI summary

Disclosed pharmaceutical compositions including a Beta site APP Cleaving Enzyme (BACE1) inhibitor and an metabotropic glutamate receptor (mGluR) agonist, and methods for use of such compositions to treat Alzheimer's disease (AD), Down's syndrome, Parkinson's disease, vascular dementia, Dementia with Lewy Bodies, dementia, and/or frontal temporal dementia.