Vagus nerve stimulation to treat neurodegenerative disorders
Inventors
Levine, Jacob A. • HAMLIN, Nicole • Chernoff, David
Assignees
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Publication Number
US-12172017-B2
Publication Date
2024-12-24
Expiration Date
Abstract
Systems, devices, and methods for using vagus nerve stimulation to treat demyelination disorders and/or disorder of the blood brain barrier are described. The vagus nerve stimulation therapy described herein is configured to reduce or prevent demyelination and/or promote remyelination to treat various disorders related to demyelination, such as multiple sclerosis. A low duty cycle stimulation protocol with a relatively short on-time and a relatively long off-time can be used.
Core Innovation
The invention provides vagus nerve stimulation (VNS) therapy aimed at reducing demyelination and promoting remyelination, including in connection with multiple sclerosis (MS). A system is described that can be implantable or non-invasive, and can include low duty-cycle stimulation having short on-time and long off-time scheduling. The stimulation is applied to the vagus nerve to affect nerves within a patient, with optional biosensing used to trigger or adjust stimulation based on detected biomarkers for demyelination.
The described control approach uses a biosensor configured to detect one or more biomarkers for demyelination and a controller with control logic to determine whether to activate stimulation based on the detected biomarker level exceeding or falling below a predetermined threshold indicative of demyelination. The therapy is associated with anti-inflammatory cholinergic pathways and dependence on α7 nicotinic acetylcholine receptors (α7 nAChR).
The document further associates the therapy with reductions in demyelination and inflammation-related indicators in a preclinical LPC-induced demyelination model. Reported outcomes include reduced lesion volume at peak demyelination, accelerated remyelination over subsequent timepoints, reduced blood–brain barrier leakiness assessed by Evans blue, reduced immune-cell infiltration, and increased pro-resolving lipid mediator Resolvin D1 (RvD1). An example system architecture includes a controller, a stimulator/pulse generator, and an optional biosensor, along with power and communications.
Claims Coverage
The independent claims cover an implantable system and methods that reduce demyelination and/or increase remyelination by stimulating a vagus nerve based on biosensor-detected demyelination biomarkers crossing a predetermined threshold. Across the independent claims, the inventive features focus on biosensor-guided vagus nerve activation and control logic, with additional independent coverage for treating a demyelination disorder and applying low duty-cycle electrical stimulation.
Biosensor-guided vagus nerve stimulation based on biomarker threshold
An implantable system comprising a biosensor configured to detect one or more biomarkers for demyelination; a stimulator configured to apply stimulation to the vagus nerve; and a controller coupled to the stimulator, the controller comprising control logic to control activation of the stimulator sufficient to reduce demyelination and/or increase remyelination when the control logic determines that the biosensor detects a biomarker for demyelination at a level exceeding or falling below a predetermined threshold indicative of demyelination.
Method of reducing demyelination and/or increasing remyelination using biosensor-triggered vagus nerve stimulation
A method comprising receiving data from a biosensor indicative of detecting a biomarker for demyelination; determining a level of the biomarker for demyelination; and applying stimulation to a vagus nerve from a stimulator when the biosensor detects the level of the biomarker for demyelination that exceeds or falls below a predetermined threshold that indicates demyelination, to reduce demyelination and/or increase remyelination of nerves within a patient.
Treating a demyelination disorder by applying vagus nerve stimulation when biosensor data crosses threshold
A method of treating a demyelination disorder comprising receiving data from a biosensor indicative of demyelination in a patient; and applying stimulation to a vagus nerve from a stimulator when the data from the biosensor is at a level that exceeds or falls below a predetermined threshold that indicates demyelination to decrease demyelination and/or to increase remyelination of the patient's nerves.
Low duty-cycle electrical vagus nerve stimulation under biomarker threshold control
An implantable system comprising a biosensor configured to detect one or more biomarkers for demyelination; a stimulator configured to apply stimulation to the vagus nerve; and a controller coupled to the biosensor and the stimulator, the controller comprising control logic configured to apply a low duty-cycle electrical stimulation of less than 5 mA to the vagus nerve from the stimulator when the control logic determines that the biosensor detects the one or more biomarkers at a level that exceeds or falls below a predetermined threshold indicating demyelination.
Across the independent claims, the core inventive coverage is biosensor-based detection of demyelination biomarkers, with control logic that activates vagus nerve stimulation when the biomarker level exceeds or falls below a predetermined threshold, to reduce demyelination and/or increase remyelination; one independent claim further specifies low duty-cycle electrical stimulation with a less-than-5 mA constraint.
Stated Advantages
Reduces demyelination (reduced lesion volume at peak demyelination in a preclinical LPC-induced demyelination model).
Increases remyelination (accelerates remyelination over subsequent timepoints in a preclinical LPC-induced demyelination model).
Reduces blood–brain barrier leakiness (Evans blue reduction in a preclinical LPC-induced demyelination model).
Reduces immune-cell infiltration (reduced immune-cell infiltration in a preclinical LPC-induced demyelination model).
Increases pro-resolving lipid mediator Resolvin D1 (RvD1) (reported increase in a preclinical LPC-induced demyelination model).
Documented Applications
Treatment of multiple sclerosis (MS) via vagus nerve stimulation therapy aimed at reducing demyelination and promoting remyelination.
Use in a preclinical LPC-induced demyelination model for evaluating effects on demyelination, remyelination, blood–brain barrier leakiness, immune-cell infiltration, and Resolvin D1.
Treatment of a demyelination disorder in a patient diagnosed with or at risk of a disorder involving demyelinated nerves.
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