Non-invasive treatment of neurodegenerative diseases

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.

1 . A method for treating an autoimmune disease or disorder in a patient, the method comprising:
 positioning a contact surface of a housing in contact with an outer skin surface of a neck of the patient;   transmitting an electric current transcutaneously and non-invasively from the contact surface through the outer skin surface to generate an electrical impulse at or near a selected nerve within the patient; and   modulating the electric current such that the electrical impulse comprises bursts of pulses with each of the bursts comprising a frequency from about 5 Hz to about 100 Hz and with each of the pulses comprising a duration from about 50 microseconds to about 1000 microseconds and such that the electrical impulse inhibits inflammation and thereby treats the autoimmune disease or disorder.   
     
     
         2 . The method of  claim 1 , wherein the housing comprises an energy source to generate the electric current before the electric current is transmitted. 
     
     
         3 . The method of  claim 1 , wherein the electrical impulse increases an activity of an anti-inflammatory cytokine in the patient and thereby treats the autoimmune disease or disorder. 
     
     
         4 . The method of  claim 1 , wherein the transmitting comprises generating a magnetic field exterior to the patient, wherein the magnetic field induces the electrical impulse at or near the selected nerve within the patient. 
     
     
         5 . The method of  claim 1 , wherein the electrical impulse stimulates a nerve fiber that controls or mediates an activity of a neurotrophic factor and thereby treats the autoimmune disease or disorder. 
     
     
         6 . The method of  claim 1 , wherein the autoimmune disease or disorder is selected from a group comprising multiple sclerosis, acute disseminated encephalomyelitis, transverse myelitis, chronic inflammatory demyelinating polyneuropathy, Guillain-Barré Syndrome, central pontine myelinosis, leukodystrophy, and Charcot Marie Tooth disease. 
     
     
         7 . The method of  claim 1 , wherein the selected nerve is a vagus nerve. 
     
     
         8 . The method of  claim 5 , wherein the neurotrophic factor is a member of a transforming growth factor (TGF) beta superfamily of a plurality of neurotrophic factors. 
     
     
         9 . The method of  claim 8 , wherein the neurotrophic factor is a member of a nerve growth factor superfamily, a neurokine superfamily, or an insulin-like family of a plurality of non-neuronal growth factors. 
     
     
         10 . The method of  claim 1 , wherein the electrical impulse inhibits a release of a pro-inflammatory cytokine and thereby treats the autoimmune disease or disorder. 
     
     
         11 . The method of  claim 11 , wherein the pro-inflammatory cytokine is tumor necrosis factor (TNF)-alpha. 
     
     
         12 . The method of  claim 1 , wherein the transmitting comprises generating an electric current and transmitting the electric current to a vagus nerve of the patient, wherein the selected nerve includes the vagus nerve. 
     
     
         13 . The method of  claim 1 , wherein the electrical impulse increases an anti-inflammatory competence of a cytokine in the patient and thereby treats the autoimmune disease or disorder. 
     
     
         14 . The method of  claim 13 , wherein the cytokine is tumor growth factor (TGF)-beta. 
     
     
         15 . The method of  claim 13 , wherein a retinoid or a component of a retinoic acid-signaling system biases a competence of the cytokine towards anti-inflammation. 
     
     
         16 . A method of treating an autoimmune disease or disorder in a patient, the method comprising:
 applying an energy transcutaneously through an outer skin surface of a patient such that an electrical impulse is generated at or near a selected nerve within the patient; and   modulating the energy such that an electrical impulse inhibits inflammation and increases an anti-inflammatory competence of a cytokine in the patient and thereby treats the autoimmune disease or disorder.   
     
     
         17 . The method of  claim 16 , wherein the autoimmune disease or disorder is selected from a group comprising multiple sclerosis, acute disseminated encephalomyelitis, transverse myelitis, chronic inflammatory demyelinating polyneuropathy, Guillain-Barré Syndrome, central pontine myelinosis, leukodystrophy, and Charcot Marie Tooth disease. 
     
     
         18 . The method of  claim 16 , wherein the applying comprises transcutaneously passing an electric current through the outer skin surface of the patient. 
     
     
         19 . The method of  claim 16 , further comprising:
 generating a magnetic field exterior to the patient, wherein the magnetic field induces the electrical impulse at or near the selected nerve within the patient.   
     
     
         20 . The method of  claim 16 , wherein the electrical impulse increases an activity of an anti-inflammatory cytokine in the patient. 
     
     
         21 . The method of  claim 16 , wherein the electrical impulse stimulates a nerve fiber that controls or mediates an activity of a neurotrophic factor. 
     
     
         22 . The method of  claim 21 , wherein the neurotrophic factor is a member of a transforming growth factor (TGF) beta superfamily of a plurality of neurotrophic factors. 
     
     
         23 . The method of  claim 21 , wherein the neurotrophic factor is a member of a nerve growth factor superfamily, a neurokine superfamily, or an insulin-like family of a plurality of non-neuronal growth factors. 
     
     
         24 . The method of  claim 16 , wherein the electrical impulse inhibits a release of a pro-inflammatory cytokine. 
     
     
         25 . The method of  claim 24 , wherein the pro-inflammatory cytokine is a tumor necrosis factor (TNF)-alpha. 
     
     
         26 . The method of  claim 16 , wherein the selected nerve is a vagus nerve. 
     
     
         27 . The method of  claim 16 , wherein the electrical impulse comprises bursts of about 2 pulses to about 20 pulses with each of the bursts having a frequency of about 5 Hz to about 100 Hz. 
     
     
         28 . The method of  claim 27 , wherein each of the pulses has a duration of about 50 microseconds to about 100 microseconds.