GABAB Upregulator Therapy for Acquired Cognitive Deficits

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Solution Overview

Problem

There is a lack of effective therapeutic options for patients with acquired cognitive deficits resulting from brain injuries or chronic diseases, as existing treatments fail to adequately restore neuronal circuits responsible for cognitive function, leading to persistent cognitive impairments and significant quality of life and economic burdens.

Innovation Solution

Administering an upregulator of gamma-aminobutyric acid B (GABAB) signaling, such as sodium oxybate, in combination with anterior-forebrain stimulating therapies like deep brain stimulation, to improve wakeful functions and sleep architecture in subjects with acquired cognitive deficiencies.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing treatments are used for acquired cognitive deficits, then treatment options are limited, but therapeutic effectiveness is insufficient

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidtreatment options

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent changes the pharmacological parameter by using GABAB receptor upregulators instead of conventional treatments. This parameter change in neurotransmitter system targeting provides both improved therapeutic effectiveness for cognitive deficits and adaptability through multiple available GABAB upregulators including baclofen, tiagabine, lesogaberan, GS-39783, zolpidem, midazolam, and sodium oxybate

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent applies a universal treatment approach using GABAB upregulators that can address multiple cognitive deficit conditions (traumatic brain injury, stroke, neurodegenerative diseases) with a single mechanism of action, thereby expanding treatment options while maintaining therapeutic effectiveness across different etiologies

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Reliability

If GABAB upregulators are administered alone, then cognitive function may improve, but sleep architecture remains disrupted

Engineering Contradiction:

Improvecognitive function improvementVSAvoidsleep architecture

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent implements periodic action by administering GABAB upregulators specifically during sleep periods (nighttime administration). This timing allows the drug to enhance slow wave sleep and sleep spindle activity during the sleep phase, thereby improving sleep architecture stability while the upregulator's effects carry over to improve cognitive function during subsequent wakeful periods

Inventive Principle:

Principle #19Periodic action

Solution Approach 2:

The patent applies preliminary action by administering the GABAB upregulator before the subject wakes up, during the sleep phase. This preliminary administration during sleep allows the neurotransmitter system to be modulated in advance, preparing the neuronal circuits for improved cognitive function during the upcoming wakeful period while simultaneously normalizing sleep architecture

Inventive Principle:

Principle #10Preliminary action

3Reliability

If anterior-forebrain stimulating therapy is used, then wakeful function improves, but treatment complexity increases

Engineering Contradiction:

Improvewakeful function improvementVSAvoidtreatment protocol

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent uses GABAB upregulators as an intermediary substance that mediates the effect on wakeful functions. Instead of directly stimulating the anterior forebrain with complex electrical devices, the pharmacological intermediary (GABAB upregulator) naturally modulates the same neuronal circuits, achieving wakeful function improvement through a simpler administrative protocol while maintaining the therapeutic mechanism

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 approach enhances wakeful functions by improving perceptual awareness, memory, and executive functions while also normalizing sleep features like slow wave modulation and REM sleep, effectively addressing cognitive deficits and sleep disturbances.

Implementation Method 1

administering to the subject an effective amount of an upregulator of gamma-aminobutyric acid B (GABAB) signaling, thereby improving the wakeful function in the subject

Methodology Applied

Scientific EffectGABAB signaling:

Implementation Method 2

the upregulator of GABAB signaling comprises electrical stimulation of corticothalamic/thalamocortical afferents in the subject

Methodology Applied

Scientific EffectElectrical stimulation:

Data Source

PatentUS20230067194A1Method for treatment of acquired cognitive deficits

Publication Date: 2023.03.02 CORNELL UNIVERSITY

AI summary

The present disclosure is directed to methods for improving a wakeful function in a subject suffering from an acquired cognitive deficiency by administering to the subject an effective amount of an upregulator of GABAB signaling, thereby improving the wakeful function in the subject. Another aspect of the disclosure us directed to methods for improving a wakeful function in a subject suffering from an acquired cognitive deficiency by administering to the subject an effective amount of an upregulator of GABAB signaling at night, in combination with administering an anterior-forebrain stimulating therapy when the subject is awake, thereby improving the wakeful function in the subject.