NON-INVASIVE TREATMENT OF NEURODEGENERATIVE DISEASES
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 methods and devices transmit an electrical impulse transcutaneously through an outer skin surface of the patient to modulate activity of a selected nerve at the target region to inhibit inflammation, enhance an anti-inflammatory competence of a cytokine in the patient and treat the neurodegenerative disorder. 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.
1 . 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, wherein the power source generates an energy field sufficient to transmit an electrical impulse transcutaneously through an outer skin surface of the patient at or near a target region sufficient to modulate activity of a selected nerve at the target region to inhibit inflammation, enhance an anti-inflammatory competence of a cytokine in the patient and treat the neurodegenerative disorder.
2 . The apparatus of claim 1 further comprising a conduction medium, wherein the source of energy generates an electric field that induces an electrical current sufficient to pass through the outer skin surface of the patient.
3 . The apparatus set forth in claim 1 wherein the electrical field has an amplitude of greater than 10 V/m.
4 . The apparatus set forth in claim 1 wherein the electrical field has a gradient of greater than 2 V/m/mm.
5 . The apparatus set forth in claim 1 wherein the electrical field comprises bursts of pulses with a frequency of 5 Hz to 100 Hz.
6 . The apparatus set forth in claim 1 wherein the electrical field comprises bursts of between 1 and 20 pulses with each pulse 50-1000 microseconds in duration.
7 . The apparatus set forth in claim 1 wherein the electrical impulse is sufficient to inhibit release of a pro-inflammatory cytokine.
8 . The apparatus set forth in claim 7 wherein the pro-inflammatory cytokine is tumor necrosis factor (TNF)-alpha.
9 . The apparatus set forth in claim 7 wherein the cytokine is tumor growth factor (TGF)-beta.
10 . The apparatus set forth in claim 1 wherein a retinoid or a component of a retinoic acid signaling system biases the competence of the cytokine towards anti-inflammation.
11 . The apparatus set forth in claim 1 wherein the electrical impulse is sufficient to enhance anti-inflammatory activity of a neurotrophic factor.
12 . The apparatus set forth in claim 11 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.
13 . The apparatus set forth in claim 1 wherein the selected nerve is a vagus nerve of the patient.
14 . The apparatus set forth in claim 1 wherein the neurodegenerative disease is Alzheimer's disease, Parkinson's disease, multiple sclerosis, postoperative cognitive dysfunction or postoperative delirium.
15 . A method for treating a neurodegenerative 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, wherein the housing
comprises an energy source;
transmitting, via the contact surface, an electric current transcutaneously and non-invasively through the outer skin surface of
the neck of the patient 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 is sufficient to increase an activity of an anti-inflammatory cytokine in the patient to inhibit an inflammation and thereby treat the neurodegenerative disorder.
16 . The method of claim 15 , wherein the electrical impulse is sufficient to stimulate a nerve fiber that controls or mediates an activity of a neurotrophic factor.
17 . The method of claim 16 , wherein the neurotrophic factor is a member of a transforming growth factor (TGF) beta superfamily of neurotrophic factors.
18 . The method of claim 16 , wherein the neurotrophic factor is a member of at least one of a nerve growth factor superfamily, a neurokine superfamily, or an insulin-like family of non-neuronal growth factors.
19 . The method of claim 16 , wherein the neurotrophic factor is a member of a same family as at least one of a nerve growth factor (NGF), a glial-cell-line-derived neurotrophic factor (GDNF), a brain-derived neurotrophic factor (BDNF), or a mesencephalic astrocyte-derived neurotrophic factor (MANF).
20 . The method of claim 15 , wherein the neurodegenerative disorder is selected from a group comprising at least one of Alzheimer's disease, Parkinson's disease, multiple sclerosis, postoperative cognitive dysfunction, or postoperative delirium.
21 . The method of claim 15 wherein the selected nerve is a vagus nerve.
22 . The method of claim 21 wherein the selected nerve is a right branch of the vagus nerve.
23 . The method of claim 15 , wherein the electrical impulse is sufficient to inhibit a release of a pro-inflammatory cytokine.
24 . The method of claim 23 wherein the pro-inflammatory cytokine is tumor necrosis factor (TNF)-alpha.
25 . The method of claim 15 wherein the selected nerve is at least approximately 1-2 cm below an outer skin surface of the patient.
26 . The method of claim 15 , wherein the electric current is modulated such that the patient has decreased measurable pain.
27 . An apparatus for applying an electric current to a target region within a patient with a neurodegenerative disorder, the
apparatus comprising:
an enclosure having a contact surface; and
a power source housed within the enclosure, wherein the power source generates an electric current sufficient to transmit an electrical impulse transcutaneously and non-invasively through an outer skin surface of a neck of the patient to a location at or near the target region when the contact surface is positioned against the outer skin surface of the neck of the patient, wherein 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 is sufficient to modulate an activity of a selected nerve at or near the target region to increase an activity of an anti-inflammatory cytokine in the patient and thereby treat the neurodegenerative disorder.
28 . The apparatus of claim 27 , further comprising a conduction medium contained within the enclosure, wherein the electrical impulse passes through the conduction medium, the contact surface, and the outer skin surface of the patient.
29 . The apparatus of claim 27 , wherein the electrical impulse is sufficient to inhibit a release of a pro-inflammatory cytokine.
30 . The apparatus of claim 29 , wherein the electrical impulse is sufficient to modulate an activity of a selected nerve at or near the target region to inhibit a release of a pro-inflammatory cytokine.
31 . The apparatus of claim 30 wherein the pro-inflammatory cytokine is tumor necrosis factor (TNF)-alpha.
32 . The apparatus of claim 27 , wherein the anti-inflammatory cytokine is transforming growth factor (TGF)-beta.
33 . The apparatus of claim 27 , wherein the selected nerve is a vagus nerve of the patient.
34 . The apparatus of claim 27 , wherein the neurodegenerative disorder comprises at least one of Alzheimer's disease, Parkinson's disease, multiple sclerosis, postoperative cognitive dysfunction, or postoperative delirium.