Vagus Nerve Stimulation for Sirtuin Modulation

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Solution Overview

Problem

Current methods for modulating sirtuins, particularly across the blood-brain barrier, are ineffective, and there is a need for a non-invasive technique to specifically target and regulate sirtuin enzymes for various therapeutic benefits without substantial impact on the neural cholinergic anti-inflammatory pathway.

Innovation Solution

Vagus nerve stimulation (VNS) is used to modulate sirtuin levels and activity, employing electrical or mechanical stimulation, with tailored parameters to enhance or suppress specific sirtuin subtypes in various tissues, including the brain, heart, skin, and liver, potentially coinciding with or independently of cholinergic anti-inflammatory pathway modulation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current methods are used to modulate sirtuins across the blood-brain barrier, then sirtuin modulation is attempted, but the methods are ineffective

Engineering Contradiction:

Improveeffectiveness of sirtuin modulationVSAvoidineffectiveness barrier

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses the vagus nerve as an intermediary pathway to deliver modulation signals to sirtuins in the brain. Instead of attempting direct delivery across the blood-brain barrier, the invention routes the modulation through the vagus nerve-stirtuin pathway, which serves as a mediator that bypasses the barrier problem entirely

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces pharmacological/chemical methods (which rely on chemical diffusion across barriers) with electrical or mechanical stimulation of the vagus nerve. This substitution of the modulation mechanism allows direct activation of sirtuins without needing to cross the blood-brain barrier chemically

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Reliability

If vagus nerve stimulation is used to modulate sirtuins, then sirtuin modulation is achieved, but there may be impact on the neural cholinergic anti-inflammatory pathway

Engineering Contradiction:

Improvesirtuin modulation effectivenessVSAvoidside effects on cholinergic pathway

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent applies local quality by using tailored stimulation parameters (frequency, amplitude, pulse width) that are specifically optimized to activate sirtuins while minimizing activation of cholinergic receptors. Different parameters are used for different therapeutic goals, creating a localized effect on sirtuins rather than broad pathway activation

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent uses partial action by applying sub-threshold or selectively-threshold stimulation that is sufficient to activate sirtuins but below the threshold for activating the cholinergic anti-inflammatory pathway. This partial activation achieves the desired sirtuin modulation without triggering unwanted side effects

Inventive Principle:

Principle #16Partial or excessive action

3Ease of operation

If non-invasive vagus nerve stimulation is used, then accessibility and safety are improved, but precise targeting of specific sirtuin subtypes may be challenging

Engineering Contradiction:

Improvenon-invasive accessibilityVSAvoidspecificity of sirtuin subtype targeting

Core Design Contradiction:

Ease of operationVSManufacturing precision

Solution Approach 1:

The patent uses dynamic parameter adjustment where frequency, amplitude, and pulse width are varied over time or across different stimulation sessions. This dynamic approach allows selective activation of different sirtuin subtypes (SIRT1, SIRT2, SIRT3) by tuning parameters to match their specific activation thresholds and response characteristics

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The patent achieves specificity through parameter changes by systematically varying electrical stimulation parameters (frequency from 1-100 Hz, amplitude from micro to milliamps, pulse width from microseconds to milliseconds) to selectively target different sirtuin subtypes. Each sirtuin subtype responds optimally to specific parameter ranges, enabling precise non-invasive targeting

Inventive Principle:

Principle #35Parameter changes

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

VNS effectively modulates sirtuin expression and activity, offering therapeutic benefits for conditions such as cancer, metabolic syndromes, neurological disorders, and inflammation, with the potential for sustained effects and reduced side effects by optimizing stimulation parameters and using feedback mechanisms.

Implementation Method 1

Vagus nerve stimulation (VNS) is used to modulate sirtuin levels and activity, employing electrical or mechanical stimulation

Methodology Applied

Scientific EffectElectrical stimulation: Electrical Impedance Tomography

Data Source

PatentUS9833621B2Modulation of sirtuins by vagus nerve stimulation

Publication Date: 2017.12.05 SETPOINT MEDICAL CORP

AI summary

Systems, devices and methods for modulation of sirtuins by neurostimulation. In particular, sirtuins may be modulated by stimulation of the vagus nerve. Further described herein generally are methods, systems and devices, for specifically modulating sirtuins, including sub-sets (types or localized regions) of sirtuins by vagus nerve stimulation (VNS).