NON-INVASIVE TREATMENT OF NEURODEGENERATIVE DISEASES

• US 20140357936A1
• Filed: 08/19/2014
• Published: 12/04/2014
• Est. Priority Date: 03/20/2009
• Status: Active Grant

• Current Assignee: Electrocore, Llc
• Original Assignee: Electrocore, Llc
• Inventors: Simon, Bruce J., Errico, Joseph P., Raffle, John T.
• Granted Patent: US 10,265,523 B2
• Time in Patent Office: Days
• US Class Current: 600/13
• 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 to the patient to generate an electrical impulse at or near a selected nerve within the patient; and

modulating the energy such that the electrical impulse is sufficient to increase an activity of anti-inflammatory cytokines in the patient to inhibit inflammation and treat the neurodegenerative disorder.

2. The method of claim 1 wherein the applying energy 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 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 stimulate nerve fibers that control or mediate activity of a neurotrophic factor.

5. 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.

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

7. The method of claim 6 wherein the selected nerve is a right branch of the vagus nerve.

8. The method of claim 4 wherein the neurotrophic factor is a member of the transforming growth factor (TGF) beta superfamily of neurotrophic factors.

9. The method of claim 4 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.

10. The method of claim 4 wherein the neurotrophic factor is a member of the same family as nerve growth factor (NGF), glial-cell-line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), or mesencephalic astrocyte-derived neurotrophic factor (MANF).

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

12. The method of claim 11 wherein the pro-inflammatory cytokine is tumor necrosis factor (TNF)-alpha.

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

generating a time-varying magnetic field that is located 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.

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

15. The method of claim 14 wherein the generating comprises generating the time-varying magnetic field within a first enclosed coil.

16. The method of claim 1 wherein the generating comprises generating an electric current and transmitting the electric current to the vagus nerve of the patient.

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

an enclosure; and

a power source housed within the enclosure and configured to generate an energy field that is sufficient to generate an electrical impulse at or near the target region sufficient to modulate activity of a selected nerve at the target region to increase an activity of anti-inflammatory cytokines in the patient and treat the neurodegenerative disorder.

18. The apparatus of claim 17 wherein the power source is configured to transmit the energy field transcutaneously through an outer skin surface of the patient to the selected nerve.

19. The apparatus of claim 17 further comprising a conduction medium, wherein the power energy is configured to generate an electric field that induces an electrical current sufficient to pass through the outer skin surface of the patient.

20. The apparatus set forth in claim 17 wherein the electrical impulse is sufficient to inhibit release of a pro-inflammatory cytokine.

21. The apparatus set forth in claim 20 wherein the pro-inflammatory cytokine is tumor necrosis factor (TNF)-alpha.

22. The apparatus set forth in claim 20 wherein the cytokine is tumor growth factor (TGF)-beta.

23. The apparatus set forth in claim 22 wherein a retinoid or a component of a retinoic acid signaling system biases the competence of the cytokine towards anti-inflammation.

24. The apparatus set forth in claim 17 wherein the electrical impulse is sufficient to enhance anti-inflammatory activity of a neurotrophic factor.

25. The apparatus set forth in claim 24 wherein the neurotrophic factor is a member of the transforming growth factor (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.

26. The apparatus set forth in claim 17 wherein the selected nerve is a vagus nerve of the patient.

27. The apparatus set forth in claim 19 wherein the electrical field has an amplitude of greater than about 10 V/m.

28. The apparatus set forth in claim 19 wherein the electrical field has a gradient of greater than about 2 V/m/mm.

29. The apparatus set forth in claim 17 wherein the energy field comprises bursts of pulses with a frequency of about 5 Hz to about 100 Hz.

30. The apparatus set forth in claim 29 wherein the energy field comprises bursts of from 1 to 20 pulses with each pulse about 50-1000 microseconds in duration.

31. The apparatus of claim 17 wherein the power source is configured to generate an electric current and to transmit the electric current through an outer skin surface of the patient to the selected nerve.

32. The apparatus set forth in claim 17 wherein the neurodegenerative disease is Alzheimer'"'"'s disease, Parkinson'"'"'s disease, multiple sclerosis, postoperative cognitive dysfunction or postoperative.