VAGUS NERVE STIMULATION TO TREAT NEURODEGENERATIVE DISORDERS

• US 20190111263A1
• Filed: 10/11/2018
• Published: 04/18/2019
• Est. Priority Date: 05/09/2011
• Status: Active Application

• Current Assignee: Setpoint Medical Corporation
• Original Assignee: Setpoint Medical Corporation
• Inventors: LEVINE, Jacob A., HAMLIN, Nicole, CHERNOFF, David
• Application Number:
  US16/158,222
• Publication Number:
  US 20190111263A1
• Time in Patent Office: Days
• CPC Class Codes: A61B 5/01 Measuring temperature of body parts ; Diagnostic temperature sensing, e.g. for malignant or inflamed tissue clinical contact thermometers G01K13/20
• CPC Class Codes: A61B 5/145 Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissuemeasuring of blood pressure or blood flow A61B5/02; non-radiation detecting or locating of foreign bodies in blood A61B5/06
• CPC Class Codes: A61B 5/24 Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
• CPC Class Codes: A61B 5/388 Nerve conduction study, e.g. detecting action potential of peripheral nerves
• CPC Class Codes: A61B 5/4029 for evaluating the peripheral nervous systems A61B5/24 takes precedence
• CPC Class Codes: A61B 5/4041 Evaluating nerves condition
• CPC Class Codes: A61B 5/4076 Diagnosing or monitoring particular conditions of the nervous system A61B5/4821, A61B5/4824 take precedence
• CPC Class Codes: A61B 5/4842 Monitoring progression or stage of a disease
• CPC Class Codes: A61B 5/6877 Nerve
• CPC Class Codes: A61N 1/0456 Specially adapted for transcutaneous electrical nerve stimulation [TENS]
• CPC Class Codes: A61N 1/0556 Cuff electrodes
• CPC Class Codes: A61N 1/08 Arrangements or circuits for monitoring, protecting, controlling or indicating for external stimulators A61N1/3603; for implantable neurostimulators A61N1/36128; for heart stimulators A61N1/37; for defibrillators A61N1/3925
• CPC Class Codes: A61N 1/36053 adapted for vagal stimulation A61N1/36114 takes precedence
• CPC Class Codes: A61N 1/36064 Epilepsy
• CPC Class Codes: A61N 1/36067 Movement disorders, e.g. tremor or Parkinson disease stimulating motor muscle A61N1/36003
• CPC Class Codes: A61N 1/36082 Cognitive or psychiatric applications, e.g. dementia or Alzheimer's disease
• CPC Class Codes: A61N 1/36103 Neuro-rehabilitation; Repair or reorganisation of neural tissue, e.g. after stroke
• CPC Class Codes: A61N 1/36175 Pulse width or duty cycle
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2333/78 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
• CPC Class Codes: G01N 2800/2835 : Movement disorders, e.g. Parkinson, Huntington, Tourette
• CPC Class Codes: G01N 2800/285 : Demyelinating diseases; Multipel sclerosis
• CPC Class Codes: G01N 2800/52 : Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 2800/7095 : Inflammation
• CPC Class Codes: G01N 33/6896 : Neurological disorders, e.g. Alzheimer's disease

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.

Claims

1. A system for reducing demyelination and/or increase remyelination by stimulation of a vagus nerve, the system comprising:

a biosensor configured to detect one or more biomarkers;

a stimulator configured to apply stimulation to the vagus nerve; and

a controller coupled to the biosensor and the stimulator and configured to apply stimulation to the vagus nerve from the stimulator sufficient to reduce demyelination and/or increase remyelination of nerves within the patient when the biosensor detects a biomarker indicative of demyelination.

2. The system of claim 1, wherein the biosensor is configured to detect a marker from the patient'"'"'s blood and/or cerebrospinal fluid.

3. The system of claim 1, wherein the biosensor is configured to detect temperature.

4. The system of claim 1, wherein the system is configured to be implanted.

5. The system of claim 1, wherein the controller is configured to apply a low duty-cycle electrical stimulation of between about 0.25 mA and about 5 mA to the vagus nerve.

6. The system of claim 1, wherein the controller is configured to apply a low duty-cycle electrical stimulation, followed by an off-time of at least 10 minutes.

7. The system of claim 1, wherein the controller is configured to apply a low duty-cycle electrical stimulation for less than about 2 minutes.

8. The system of claim 1, wherein the controller is configured to apply a low duty-cycle electrical stimulation of between about 0.25 mA and about 5 mA to the vagus nerve for less than about 2 minutes, followed by an off-time of at least 10 minutes.

9. The system of claim 1, wherein the stimulator comprises an electrode configured to apply electrical energy to the vagus nerve.

10. The system of claim 1, further comprising a nerve cuff configured to secure the stimulator to the vagus nerve.

11. A method of reducing demyelination in a patient diagnosed with or at risk of a disorder involving demyelinated nerves, the method comprising detecting a marker for demyelination and applying stimulation to the vagus nerve to reduce demyelination of nerves within the patent.

12. The method of claim 11, wherein applying comprises applying a low duty-cycle electrical stimulation of between about 0.25 mA and about 5 mA to the vagus nerve.

13. The method of claim 11, wherein applying comprises applying a low duty-cycle electrical stimulation, followed by an off-time of at least 10 minutes.

14. The method of claim 11, wherein applying comprises applying a low duty-cycle electrical stimulation for less than about 2 minutes.

15. The method of claim 11, wherein applying comprises applying electrical stimulation of between about 0.25 and about 5 mA to the vagus nerve for less than about 2 minutes, followed by an off-time of at least 10 minutes.

16. The method of claim 11, further comprising applying non-invasive stimulation to the vagus nerve.

17. The method of claim 11, further comprising continuously monitoring the patient for the marker.

18. The method of claim 11, wherein detecting a marker for demyelination comprises monitoring the patient'"'"'s temperature.

19. The method of claim 11 wherein detecting a marker for demyelination comprises determining a level of tumor necrosis factor in a blood or cerebrospinal fluid sample.

20. The method of claim 11, further comprising diagnosing or identifying a patient suffering from a disorder involving demyelinated nerves.

21. A method of treating a demyelination disorder, the method comprising:

detecting demyelination in a patient, and applying stimulation to the vagus nerve to increase the remyelination of nerves within the patent.

22. The method of claim 21, further comprising repeatedly applying a low duty-cycle electrical stimulation of between about 0.25 and about 5 mA to the patient'"'"'s vagus nerve for less than about 2 minutes, followed by an off-time of between about 12 and about 48 hours.

23. The method of claim 21, further comprising concurrently treating with a pharmacological agent.

24. The method of claim 21, further comprising continuously monitoring the patient for demyelination.

25. The method of claim 21, further comprising monitoring the patient for a marker related to a diseased selected from the group consisting of neurodegenerative diseases, neuroinflammatory diseases, and neuropathies.

26. The method of claim 21, wherein detecting demyelination in a patient comprises detecting a marker is related to multiple sclerosis.

27. The method of claim 26, wherein the marker is selected from the group consisting of neurofilament, glial fibrillary acidic protein, the monocyte macrophage marker CD163, the glial activation marker YKL-40, the B cell chemoattractant CXCL13, miRNA, mRNA, myelin reactive t cells, Kir4.1 antibodies, osteopontin, and microbiome associated lipopeptides.