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CN-122003270-A - Systems and methods for modulating the nervous immune system

CN122003270ACN 122003270 ACN122003270 ACN 122003270ACN-122003270-A

Abstract

Methods and systems for modulating a neuroimmune response while monitoring biomarkers that may be directly or indirectly related to neuroimmune function. Neuromodulation therapy may be delivered and biomarker levels may be determined. Some biomarker levels are determined from body fluids collected from a patient and compared to a predetermined threshold level. One or more electrode leads and/or optical fibers are used to deliver therapeutic stimulation to a patient.

Inventors

  • GU JIANWEN
  • Bradley Lawrence Helche
  • ZHU CHANGFANG

Assignees

  • 波士顿科学神经调制公司

Dates

Publication Date
20260508
Application Date
20241008
Priority Date
20231009

Claims (15)

  1. 1. A system for optimizing a neural therapy for a neural immune system function, the system comprising: an output circuit housed by the implantable pulse generator configured to deliver neural therapy; a sensor for sensing the level of one or more biomarkers in a patient; The controller is used for controlling the operation of the controller, the controller is configured to: Instruct the output circuit to deliver a first neural therapy; Instructing the sensor to measure the level of the one or more biomarkers after the first neural therapy is emitted by the implantable pulse generator; Comparing the measured post-neuromodulation level of the one or more biomarkers to a threshold value, and If the measurement exceeds the threshold, the output circuit is instructed to deliver a second neural therapy.
  2. 2. The system of claim 1, wherein the implantable pulse generator comprises the sensor and the controller.
  3. 3. The system of claim 1, wherein the controller is housed in the implantable pulse generator and the sensor is separate from the implantable pulse generator and in communication with the controller.
  4. 4. The system of claim 1, wherein the controller is located in an external device having communication circuitry for communicating with the implantable pulse generator, optionally wherein the sensor is part of the external device.
  5. 5. The system of claim 1, wherein the neural therapy comprises an electrical pulse.
  6. 6. The system of claim 1, wherein the neural therapy comprises an optical signal.
  7. 7. The system of any one of claims 5 or 6, further comprising a lead coupled to the pulse generator and adapted to extend from the pulse generator to a target nerve tissue, wherein: The lead includes one or more electrodes for outputting electrical pulses, and/or The leads include optical transducers for generating an optical output from an electrical signal emitted by the output circuit, and/or The lead includes an optical fiber for transmitting an optical signal from the output circuit.
  8. 8. The system of any one of claims 1 to 7, wherein the measurement is an amplitude of the biomarker and the threshold is a population-based threshold of a normal level of the one or more biomarkers.
  9. 9. The system of any one of claims 1 to 7, wherein the measurement is an amplitude of the biomarker and the threshold is a patient-specific reference of the biomarker.
  10. 10. The system of any one of claims 1 to 7, wherein the measurement is a trend of the biomarker.
  11. 11. The system of any preceding claim, wherein the sensor is configured to analyze body fluid in situ and the body fluid is one of interstitial fluid, blood, cerebrospinal fluid or intrathecal fluid.
  12. 12. The system of any one of claims 1 to 11, wherein the one or more biomarkers comprise spleen tyrosine kinase.
  13. 13. The system of any one of claims 1 to 11, wherein the one or more biomarkers comprise resolvins D1.
  14. 14. The system of any one of claims 1 to 11, wherein the one or more biomarkers are selected from a pro-inflammatory mediator, an anti-inflammatory mediator, an immune cell, or a resolvinal compound.
  15. 15. The system of any one of claims 1 to 11, wherein the implantable pulse generator comprises circuitry for measuring electrical signals from a brain of a patient to determine an intrinsic gamma frequency of the patient, and the step of delivering neural therapy to the patient comprises issuing electrical pulses at a repetition rate determined from the intrinsic gamma frequency of the patient.

Description

Systems and methods for modulating the nervous immune system Cross Reference to Related Applications The present application claims the benefit of U.S. provisional patent application Ser. No. 63/543,193, filed on 10/9 of 2023, the disclosure of which is incorporated herein by reference. Background Many diseases involve neuroinflammation. Current medical treatments for neuroinflammation are mainly pharmacological, such as the use of anti-inflammatory drugs for cytokine inhibition or microglial inhibition. Studies have shown that neuromodulation can modulate the neuroimmune system. Historically, neuromodulation therapies have not been optimized to reduce neuroinflammation. There is currently interest in optimizing neuromodulation therapies to target neuroimmune responses to reduce or otherwise treat neuroinflammation. Disclosure of Invention The present inventors have recognized that among other things, the problem to be solved is the need for a non-pharmacological option for treating neuroinflammation. One solution is to optimize current neuromodulation devices for modulating the function of the neuroimmune system. It is proposed to modulate neuroimmune responses with electrical stimulation alone and/or in combination with phototherapy, and to monitor neuroimmune biomarker levels. A closed loop system, such as an SCS system, is also presented that senses neuroinflammatory biomarkers in body fluids, or receives data about such biomarkers, and optimizes therapy over time. Some examples may include an implantable neuromodulation system for use in conjunction with a sensing or other diagnostic system to obtain neuroinflammatory markers, such as by measuring biomarkers using interstitial fluid, blood, CSF, or other physical interactions. The first illustrative and non-limiting example takes the form of a system for optimizing a neural therapy for a neural immune system function, the system comprising an output circuit housed by an implantable pulse generator configured to deliver the neural therapy, a sensor for sensing a level of one or more biomarkers in a patient, a controller configured to instruct the output circuit to deliver the first neural therapy, instruct the sensor to measure the level of the one or more biomarkers after the first neural therapy is delivered by the implantable pulse generator, compare a measurement of the neuromodulated level of the one or more biomarkers to a threshold, and instruct the output circuit to deliver a second neural therapy if the measurement exceeds the threshold. Additionally or alternatively, the implantable pulse generator includes a sensor and a controller. Additionally or alternatively, the controller is housed in the implantable pulse generator, and the sensor is separate from the implantable pulse generator and in communication with the controller. Additionally or alternatively, the controller is located in an external device having communication circuitry for communicating with the implantable pulse generator, optionally wherein the sensor is part of the external device. Additionally or alternatively, the nerve therapy includes an electrical pulse. Additionally or alternatively, the nerve therapy includes an optical signal. Additionally or alternatively, the system further comprises a lead coupled to the pulse generator and adapted to extend from the pulse generator to the target nerve tissue, wherein the lead comprises one or more electrodes for outputting the electrical pulse and/or the lead comprises an optical transducer for generating an optical output from the electrical signal emitted by the output circuit and/or the lead comprises an optical fiber for transmitting the optical signal from the output circuit. Additionally or alternatively, the measurement is an amplitude of the biomarker, and the threshold is a population-based threshold of a normal level of the one or more biomarkers. Additionally or alternatively, the measurement is an amplitude of the biomarker and the threshold is a patient specific reference of the biomarker. Additionally or alternatively, the measurement is a trend of the biomarker. Additionally or alternatively, the sensor is configured to analyze the bodily fluid in situ, and the bodily fluid is one of interstitial fluid, blood, cerebrospinal fluid, or intrathecal fluid. Additionally or alternatively, the one or more biomarkers include spleen tyrosine kinase. Additionally or alternatively, the one or more biomarkers comprise resolvins D1. Additionally or alternatively, the one or more biomarkers are selected from the group consisting of pro-inflammatory mediators, anti-inflammatory mediators, immune cells, or resolvins. Additionally or alternatively, the implantable pulse generator includes circuitry for measuring electrical signals from the brain of the patient to determine an intrinsic gamma frequency of the patient, and the step of delivering the neural therapy to the patient includes issuing electrical pulses at a repetition rat