Stimulation of a nerve supplying the spleen

Patent metadata

Field	Value
Publication number	US-11446502-B2
Application number	US-201816955264-A
Country	US
Kind code	B2
Filing date	Dec 20, 2018
Priority date	Dec 20, 2017
Publication date	Sep 20, 2022
Grant date	Sep 20, 2022

Abstract

Stimulation of neural activity in a nerve supplying the spleen, wherein the nerve is associated with a neurovascular bundle, can modulate pro- and anti-inflammatory molecules levels, thereby reducing inflammation and providing ways of treating inflammatory disorders. The invention provides improved ways of treating inflammatory disorders which minimize off-target effects.

First claim

The invention claimed is:

1. A system for stimulating neural activity of a nerve supplying a spleen, wherein the nerve is associated with a neurovascular bundle, the system comprising:
at least one electrode configured to be in signaling contact with the nerve supplying the spleen; and
at least one controller electrically coupled to the at least one electrode, the at least one controller configured to control operation of the at least one electrode to apply an electrical signal having a charge density to the nerve, wherein the charge density per phase applied to the nerve by the electrical signal is ≥70 μC per cm 2 per phase and >1100 μC per cm 2 per phase, the electrical signal capable of producing an improvement in a physiological parameter in a subject, wherein the improvement in the physiological parameter is one or more of the group consisting of: a reduction in pro-inflammatory cytokines, an increase in anti-inflammatory cytokines and/or pro-resolving mediators, an increase in catecholamines, changes in immune cell population or immune cell surface co-stimulatory molecules, a reduction in factors involved in an inflammation cascade, and/or a reduction in immune response mediators.

2. The system of claim 1 , where the charge density per phase is ≥70 μC per cm 2 per phase and ≤500 μC per cm 2 per phase.

3. The system of claim 1 , where the charge density per phase is ≥70 μC per cm 2 per phase and ≤250 μC per cm 2 per phase.

4. The system of claim 1 , where the charge density per phase is ≥70 μC per cm 2 per phase and ≤170 μC per cm 2 per phase.

5. The system of claim 1 , wherein the electrical signal comprises a pulse train comprising a plurality of pulses.

6. A method of determining whether a neural interface is correctly placed in signaling contact with a nerve supplying a spleen, wherein the nerve is associated with a neurovascular bundle, the method comprising:
providing the system of claim 1 ;
positioning the neural interface in signaling contact with the nerve;
controlling the operation of the at least one electrode with the at least one controller to apply an electrical signal to the nerve;
determining at least one of: blood flowrate in the spleen, blood flow rate in a splenic artery, blood flowrate in a splenic vein, spleen volume, neural activity in the nerve, or impedance of the at least one electrode; and
indicating to an operator that the neural interface had been placed correctly in signaling contact with the nerve.

7. A method of reversibly stimulating neural activity in a nerve supplying a spleen, wherein the nerve is associated with a neurovascular bundle, the method comprising:
providing the system of claim 1 ;
positioning the at least one electrode in signaling contact with the nerve; and
controlling operation of the at least one electrode with the at least one controller to apply an electrical signal to the nerve to stimulate neural activity.

8. The method of claim 7 , wherein the method is for treating inflammatory disorders in a subject.

9. The method of claim 8 , wherein the inflammatory disorder is selected from the group of: arthritis, rheumatoid arthritis, osteoarthritis, psoriatic arthritis, Grave's disease, myasthenia gravis, thryoiditis, systemic lupus erythematosus, Goodpasture's syndrome, Behcets's syndrome, allograft rejection, graft-versus-host disease, ankylosing spondylitis, Berger's disease, diabetes including Type I diabetes, Reitier's syndrome, spondyloarthropathy, psoriasis, multiple sclerosis, Inflammatory Bowel Disease, Crohn's disease, Addison's disease, autoimmune mediated hair loss, alopecia areata, and ulcerative colitis.

10. The method of claim 8 , wherein the inflammatory disorder is selected from the group of: asthma, allergy, anaphylactic shock, immune complex disease, sepsis, septicemia, endotoxic shock, eosinophilic granuloma, granulomatosis, organ ischemia, reperfusion injury, organ necrosis, hay fever, cachexia, hyperexia, septic abortion, HIV infection, herpes infection, organ transplant rejection, disseminated bacteremia, Dengue fever, malaria, and sarcoidosis.

11. The method of claim 8 , wherein the inflammatory disorder is an autoimmune disorder.

12. The method of claim 11 , wherein the autoimmune disorder is selected from the group of: rheumatoid arthritis, osteoarthritis, psoriatic arthritis, spondyloarthropathy, ankylosing spondylitis, psoriasis, systemic lupus erythematosus (SLE), multiple sclerosis, Inflammatory Bowel Disease, Crohn's disease, ulcerative colitis, and sepsis.

13. The method of claim 11 , wherein the autoimmune disorder is systemic lupus erythematosus (SLE) or rheumatoid arthritis.

Assignees

• Galvani Bioelectronics Ltd

Inventors

• Donega Matteo
• Chew Daniel John
• Gupta Isha

Classifications

• A61B5/14542

  for measuring blood gases (A61B5/14551 takes precedence) · CPC title

• A61B5/416

  the spleen · CPC title

• A61B5/0836

  Measuring rate of CO2 production · CPC title

• A61B5/01

  Measuring temperature of body parts {; Diagnostic temperature sensing, e.g. for malignant or inflamed tissue} (clinical contact thermometers G01K13/20) · CPC title

• A61N1/36178

  Burst or pulse train parameters · CPC title