NON-INVASIVE TREATMENT OF NEURODEGENERATIVE DISEASES

• US 20110152967A1
• Filed: 01/12/2011
• Published: 06/23/2011
• Est. Priority Date: 03/20/2009
• Status: Active Grant

• Current Assignee: Electrocore, Llc
• Original Assignee: Electrocore, Llc
• Inventors: Raffle, John T., Errico, Joseph P., Simon, Bruce
• Granted Patent: US 8,868,177 B2
• Time in Patent Office: Days
• US Class Current: 607/45
• CPC Class Codes: A61N 1/36025 for treating a mental or cerebral condition
• CPC Class Codes: A61N 1/36114 Cardiac control, e.g. by vagal stimulation stimulating the heart A61N1/362
• CPC Class Codes: A61N 1/40 Applying electric fields by inductive or capacitive coupling microwave apparatus A61N5/00; Applying radio-frequency signals
• CPC Class Codes: A61N 2/002 in combination with another treatment
• CPC Class Codes: A61N 2/006 for magnetic stimulation of nerve tissue
• CPC Class Codes: A61N 2/02 using magnetic fields produced by coils, including single turn loops or electromagnets A61N2/12 takes precedence

Abstract

Methods and devices are disclosed for the non-invasive treatment of neurodegenerative diseases through delivery of energy to target nervous tissue, particularly the vagus nerve. The devices include a magnetic stimulator having coils with toroidal windings, which are in contact with an electrically conducting medium that is adapted to conform to the contour of a target body surface of a patient. The coils induce an electric current and/or an electric field within the patient, thereby stimulating nerve fibers within the patient. The stimulation brings about reduction of neuroinflammation in patients suffering from conditions comprising Alzheimer'"'"'s Disease, Parkinson'"'"'s Disease, Multiple Sclerosis, postoperative cognitive dysfunction and postoperative delirium. Reduction in inflammation is effected by enhancing the anti-inflammatory competence of cytokines such as TGF-beta, wherein a retinoid or components of the retinoic acid signaling system provide an anti-inflammatory bias, by enhancing anti-inflammatory activity of a neurotrophic factor such as NGF, GDNF, BDNF, or MANF, and/or by inhibiting the activity of pro-inflammatory cytokines such as TNF-alpha.

Claims

1. A method for treating a neurodegenerative disorder in a patient comprising applying energy transcustaneously through an outer skin surface of a patient to generate an electrical impulse at or near a selected nerve within the patient sufficient to inhibit inflammation in the patient and treat the neurodegenerative disorder.

2. The method of claim 1 wherein the applying energy step is carried out by transcutaneously passing an electrical current through an outer skin surface of the patient.

3. The method of claim 1 wherein the applying energy step is carried out by generating a magnetic field exterior to the patient sufficient to induce an electrical impulse at or near the selected nerve within the patient.

4. The method of claim 1 wherein the electrical impulse is sufficient to increase an anti-inflammatory competence of cytokines.

5. The method of claim 1 wherein the electrical impulse is sufficient to increase the activity of anti-inflammatory cytokines.

6. The method of claim 1 wherein the electrical impulse is sufficient to stimulate nerve fibers that control or mediate the activity of a neurotrophic factor.

7. The method of claim 1 wherein the neurodegenerative disease is selected from a group comprising Alzheimer'"'"'s disease, Parkinson'"'"'s disease, multiple sclerosis, postoperative cognitive dysfunction or postoperative delirium.

8. The method of claim 1 wherein the selected nerve is a vagus nerve.

9. The method of claim 8 wherein the selected nerve is a right branch of the vagus nerve.

10. The method of claim 6 wherein the neurotrophic factor is a member of the TGF-beta superfamily of neurotrophic factors.

11. The method of claim 6 wherein the neurotrophic factor is a member of the nerve growth factor superfamily, the neurokine superfamily, or the insulin-like family of non-neuronal growth factors.

12. The method of claim 6 wherein the neurotrophic factor is a member of the same family as NGF, GDNF, BDNF, or MANF.

13. The method of claim 1 wherein the electrical impulse is sufficient to inhibit the release of a pro-inflammatory cytokine.

14. The method of claim 13 wherein the pro-inflammatory cytokine is TNF-alpha.

15. The method of claim 1 wherein the applying energy step is carried out by:

generating a time-varying magnetic field that is located essentially entirely outside of the patient;

shaping an electric field that is induced by said magnetic field; and

conducting an electric current that is induced by said magnetic field through an outer skin surface of the patient to modulate the selected nerve.

16. The method of claim 1 wherein the selected nerve is at least approximately 1-2 cm below an outer skin surface of the patient.

17. The method of claim 15 further comprising substantially constraining the electric current from modulating one or more nerves in a region between the outer skin surface and the selected nerve.

18. The method of claim 15 wherein the generating step comprises generating the time-varying magnetic field within an enclosed coil.

19. The method of claim 18 wherein the shaping step comprises generating a second time-varying magnetic field within a second enclosed coil positioned near or adjacent to the first enclosed coil.

20. The method of claim 15 wherein the shaping step comprises positioning a conducting medium around a portion of the enclosed coil such that the direction of the electrical field is constrained within the conducting medium.

21. The method of claim 15 wherein the conducting step is carried out by electrically coupling the induced electric field to the target region allowing current to flow through the outer skin surface of the patient.

22. An apparatus for applying energy transcutaneously to a target region within a patient with a neurodegenerative disorder, comprising:

a source of energy for generating an energy field that is located essentially entirely exterior to an outer skin surface of the patient, the energy field being sufficient to transcutaneously pass through the outer skin surface and generate an electrical impulse at or near the target region; and

wherein the electrical impulse is sufficient to modulate activity of a selected nerve at the target region to inhibit inflammation in the patient and treat the neurodegenerative disorder.

23. The apparatus of claim 22 further comprising a conduction medium, wherein the source of energy is configured to generate an electric field that induces an electrical current sufficient to pass through the outer skin surface of the patient.

24. The apparatus set forth in claim 22 wherein the electrical impulse is sufficient to inhibit release of a pro-inflammatory cytokine.

25. The apparatus set forth in claim 24 wherein the pro-inflammatory cytokine is TNF-alpha.

26. The apparatus set forth in claim 22 wherein the electrical impulse is sufficient to enhance the anti-inflammatory competence of a cytokine.

27. The apparatus set forth in claim 26 wherein the cytokine is TGF-beta.

28. The apparatus set forth in claim 26 wherein a retinoid or a component of a retinoic acid signaling system biases the competence of the cytokine towards anti-inflammation.

29. The apparatus set forth in claim 22 wherein the electrical impulse is sufficient to enhance anti-inflammatory activity of a neurotrophic factor.

30. The apparatus set forth in claim 29 wherein the neurotrophic factor is a member of the TGF-beta superfamily of neurotrophic factors, the nerve growth factor superfamily of neurotrophic factors, the neurokine superfamily of neurotrophic factors, or the insulin-like family of non-neuronal growth factors.

31. The apparatus set forth in claim 22 wherein the selected nerve is a vagus nerve of the patient.

32. The apparatus set forth in claim 23 wherein the electrical field has an amplitude of greater than 10 V/m.

33. The apparatus set forth in claim 23 wherein the electrical field has a gradient of greater than 2 V/m/mm.

34. The apparatus set forth in claim 23 wherein the electrical field comprises bursts of pulses with a frequency of about 5 Hz to about 100 Hz.

35. The apparatus set forth in claim 23 wherein the electrical field comprises bursts of between 1 and 20 pulses with each pulse about 50-1000 microseconds in duration.

36. The apparatus set forth in claim 22 wherein the neurodegenerative disease is Alzheimer'"'"'s disease, Parkinson'"'"'s disease, multiple sclerosis, postoperative cognitive dysfunction or postoperative delirium.