Group II mGluR Modulators for Sleep Spindle Deficit Treatment

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current treatments for disorders associated with sleep spindle deficits, such as schizophrenia, are inadequate in addressing the underlying neural circuitry disruptions and synaptic plasticity issues.

Innovation Solution

Administration of a pharmaceutical composition comprising a group II metabotropic glutamate receptor modulator, specifically agonists or positive allosteric modulators like LY379268 and Mavalon-63, to alter sleep spindles and rescue disrupted thalamic excitability in subjects with CACNA1I gene mutations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments are used for disorders associated with sleep spindle deficits, then general symptom management is achieved, but underlying neural circuitry disruptions and synaptic plasticity issues are not addressed

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidaddressing underlying neural mechanisms

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent changes the pharmacological parameter by using group II metabotropic glutamate receptor modulators instead of conventional treatments. This specific parameter change targets the underlying neural circuitry disruptions and synaptic plasticity issues associated with sleep spindle deficits, thereby improving both treatment effectiveness and adaptability to address root causes rather than just symptoms.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If group II metabotropic glutamate receptor modulators are administered, then sleep spindle density and thalamic reticular nucleus neuron activity are increased, but the complexity of the treatment mechanism increases

Engineering Contradiction:

Improvesleep spindle deficit treatmentVSAvoidtreatment mechanism complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The group II metabotropic glutamate receptor modulator acts as an intermediary substance that mediates between the administered drug and the neural circuitry. It binds to specific receptors in the thalamic reticular nucleus, triggering a cascade of effects that increase sleep spindle density and neuron activity. This intermediary mechanism provides a targeted and controllable way to treat sleep spindle deficits without requiring direct manipulation of complex neural circuits.

Inventive Principle:

Principle #24Intermediary (Mediator)

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 use of group II metabotropic glutamate receptor modulators increases rebound burst firing and sleep spindle density, effectively treating sleep spindle deficits and associated disorders by enhancing thalamic reticular nucleus neuron activity.

Implementation Method 1

modulation of group II metabotropic glutamate receptors can alter sleep spindles

Methodology Applied

Scientific EffectMetabotropic glutamate receptor activation:

Implementation Method 2

group II metabotropic glutamate receptor modulator

Methodology Applied

Scientific EffectG-protein coupled receptor signaling:

Data Source

PatentUS20220211658A1Methods for treating disorders associated with sleep spindle deficits

Publication Date: 2022.07.07 THE BROAD INST INC

AI summary

Provided herein are methods for treating a disorder associated with a sleep spindle deficit using a group II metabotropic glutamate receptor modulator.