WO2023069117A1 - Immunorégulation du cerveau par traitement électromagnétique transcrânien - Google Patents

Immunorégulation du cerveau par traitement électromagnétique transcrânien Download PDF

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Publication number
WO2023069117A1
WO2023069117A1 PCT/US2021/056328 US2021056328W WO2023069117A1 WO 2023069117 A1 WO2023069117 A1 WO 2023069117A1 US 2021056328 W US2021056328 W US 2021056328W WO 2023069117 A1 WO2023069117 A1 WO 2023069117A1
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brain
electromagnetic
cytokine
subject
emitters
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PCT/US2021/056328
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Gary W. Arendash
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NeuroEM Therapeutics, Inc.
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Priority to PCT/US2021/056328 priority Critical patent/WO2023069117A1/fr
Publication of WO2023069117A1 publication Critical patent/WO2023069117A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/02—Radiation therapy using microwaves
    • A61N5/022—Apparatus adapted for a specific treatment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/02—Radiation therapy using microwaves
    • A61N5/04—Radiators for near-field treatment

Definitions

  • cytokines are the immune system’s “modulators” or “effectors”. In the brain particularly, there are multiple cells that secrete cytokines to influence brain function - microglia, astrocytes, choroid plexus epithelial cells, and even neurons to some extent.
  • FIG. 1 is a block diagram of an electromagnetic treatment device, according to an example of the principles described herein.
  • Figure 2 is a flowchart of a method for normalizing or rebalancing cytokine levels in the brain and/or cerebrospinal fluid (CSF) of a subject, according to an example of the principles described herein.
  • CSF cerebrospinal fluid
  • FIGS 3A-3C depict transcranial electromagnetic treatment (TEMT) to the human head, according to an example of the principles described herein.
  • TCT transcranial electromagnetic treatment
  • Figure 4 is a graph showing the immunoregulatory/rebalancing ability of TEMT in the Alzheimer’s disease (AD) brain/CSF by displaying a strong correlation between baseline levels of the cytokine IL-17a in CSF of individual AD subjects and both the direction and extent of TEMT-induced change in IL-17a after 2 months of daily treatment.
  • AD Alzheimer’s disease
  • Figure 5 is a graph showing the immunoregulatory/rebalancing ability of TEMT in the Alzheimer’s brain/CSF by displaying a strong correlation between baseline levels of the cytokine nerve growth factor (NGF) in CSF of individual AD subjects and both the direction and extent of TEMT-induced change in NGF after 2 months of daily treatment.
  • Figure 6 is a graph showing the immunoregulatory/rebalancing ability of TEMT in the Alzheimer’s brain/CSF by displaying a strong correlation between baseline levels of the cytokine granulocyte colony-stimulating factor (GCSF) in CSF of individual AD subjects and both the direction and extent of TEMT-induced change in GCSF after 2 months of daily treatment.
  • GCSF cytokine granulocyte colony-stimulating factor
  • Figure 7 is a graph showing that the direction and change in brain/CSF levels of the cytokine GCSF induced by TEMT is strongly associated with the degree of cognitive impairment (e.g., as indexed by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) test) in individual AD subjects.
  • ADAS-Cog Alzheimer's Disease Assessment Scale-Cognitive Subscale
  • Figure 8 is a flowchart of a method for rebalancing cytokine/immune mediator levels in the brain/CSF of a subject by affecting various immune- related cell types in the brain, according to another example of the principles described herein.
  • Figure 9 is a flowchart of a method for rebalancing cytokine/immune mediator levels in the brain/CSF of a subject by affecting non-immune cells and/or mechanisms in the brain, according to another example of the principles described herein.
  • Figure 10 depicts body/peripheral electromagnetic treatment (PEMT), specifically with electromagnetic emitters located above major arterial, venous, and lymphatic vessels in the neck and axial region of the arm, as well as above the lower lung.
  • PEMT body/peripheral electromagnetic treatment
  • Figurel 1 is a flowchart of a method for increased lymph flow through meningeal lymphatic vessels in the brain to enhance clearance/removal of toxins from the brain, according to an example of the principles described herein.
  • Figure 12 is a flowchart of a method for increasing human life span (longevity) by reducing age-related diseases and/or through mechanisms independent of age-related diseases, according to an example of the principles described herein.
  • Figures 13A-13B illustrate differences between TEMT electromagnetic waves having interdigitated electric and magnetic waves and magnetic waves generated by magnets.
  • Cytokine dysregulation is believed to play a key role in remodeling of the immune system in older age. More specifically, there is an increasing, age-related inability to maintain balance between the immune system’s pro- inflammatory and anti-inflammatory components. Thus, as one ages, there is a progressive weighing toward pro-inflammatory cytokines called “inflamm- aging”. This low-level, chronic state of inflammation in brain and body appears to be a key and common element to most age-related diseases, including Alzheimer’s Disease, cancer, and cardiovascular disease.
  • meningeal lymphatic system of the brain provides a linkage between the brain and body immune components, there remains no therapeutic intervention that has the capacity to regulate/rebalance the cytokine/immune mediators in either brain or body, much less both of them in sync.
  • neuromodulatory device approaches include transcranial magnetic stimulation (tMS), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS). All three of these approaches stimulate the activity of neurons in the brain.
  • tMS transcranial magnetic stimulation
  • tDCS transcranial direct current stimulation
  • DBS deep brain stimulation
  • All three of these approaches stimulate the activity of neurons in the brain.
  • tMS transcranial magnetic stimulation
  • tDCS transcranial direct current stimulation
  • DBS deep brain stimulation
  • All three of these approaches stimulate the activity of neurons in the brain.
  • tMS transcranial magnetic stimulation
  • tDCS transcranial direct current stimulation
  • DBS deep brain stimulation
  • a balanced immune system may be the pathway to life extension/longevity.
  • centenarians have both an enhanced pro-inflammatory status and an enhanced anti-inflammatory status.
  • centenarians have a balanced, robust immune system of pro- and anti-inflammatory components that contribute to their healthy longevity.
  • a method to regulate cytokines/immune mediators in older age such that both pro- and anti-inflammatory cytokines are vigorous and balanced may prevent or even stabilize/reverse many age-related diseases of brain and body, to result in an increased life span in good health (an increased “healthspan”).
  • Transcranial Electromagnetic Treatment is a promising neuromodulatory approach against diseases of aging, such as AD.
  • Comprehensive pre-clinical studies in AD transgenic mice have shown that TEMT penetrates the brain and its neurons to “disaggregate” small aggregates/oligomers of two toxic proteins that appear to be the root causes of AD. These toxic proteins are Ap and tau.
  • the MEMOREMTM device provides full forebrain treatment with electromagnetic/ radiofrequency waves through multiple emitters distributed on the human head surface to induce electromagnetic (EM) fields in the brain.
  • EM electromagnetic
  • the MEMOREMTM device has been shown to provide considerable cognitive benefit to AD subjects, changes in their A levels within cerebrospinal fluid (CSF) consistent with Ap disaggregation in the brain, and evidence of enhanced brain function in their functional magnetic resonance imaging (fMRI) scans.
  • CSF cerebrospinal fluid
  • fMRI functional magnetic resonance imaging
  • the present specification describes the application of electromagnetic field treatment to rebalance immune function in the aging human brain and to increase human longevity. It should be noted that the described methods, systems and results of the present specification were arrived at from “human” studies (not in vitro or animal studies), and, as such, have direct applicability to humans. [0027] Accordingly, the present specification presents methods to: 1) provide immunoregulation in the human brain, as defined by the lowering of high cytokine/immune mediator levels and/or the increasing of low cytokine/immune mediator levels in the brain and/or CSF (referred to herein as “brain/CSF”), and 2) increase human life span, through such immunoregulation or otherwise in the brain and/or body.
  • brain/CSF CSF
  • the first method does not involve the influencing of any blood/plasma components going through the brain or body vasculature.
  • the term “brain” may refer to both brain tissue and the cerebrospinal fluid (CSF) in and around the brain.
  • the term “brain” may refer to brain tissue and/or CSF.
  • the present specification describes methodologies that can increase life span (longevity) of a subject (e.g., a human), in part by reducing the risk of age-related diseases and thus increasing the chances of healthy, disease-free aging.
  • a first method is provided whereby the human brain is treated with electromagnetic fields through Transcranial Electromagnetic Treatment (TEMT).
  • a second method provides electromagnetic fields to the body or periphery through peripheral electromagnetic treatment (PEMT).
  • PET Transcranial Electromagnetic Treatment
  • PEMT peripheral electromagnetic treatment
  • Figure 1 is a block diagram of an electromagnetic treatment device (100), according to an example of the principles described herein.
  • Figure 1 depicts an electromagnetic treatment device (100) that includes an array of electromagnetic emitters (102).
  • the electromagnetic emitters (102) may be positioned adjacent a head surface of the subject in, for example, a transcranial electromagnetic treatment (TEMT) device (100).
  • the electromagnetic emitters (102) are positioned adjacent a body surface of the subject in, for example, a peripheral electromagnetic treatment (PEMT).
  • the electromagnetic emitters (102) project an electromagnetic field toward the head and/or body of the subject (e.g., a patient).
  • the electromagnetic emitter(s) (102) is (are) activated to apply electromagnetic fields/treatment to the subject primarily for the remedy of diseases or conditions of immune system imbalance wherein cytokine levels are abnormally high or low.
  • electromagnetic waves may be generated by the electromagnetic wave generator (108), sent to an emitter (102), and then passed into tissue as an electromagnetic field.
  • the electromagnetic treatment device (100) may include a control interface (104), a controller (106), an electromagnetic wave generator (108), and one or more electromagnetic emitters (102) that apply the treatment to the desired portion of the brain or body.
  • the controller (106) manages the treatment and its parameters by manipulating the electromagnetic wave generator (108) and electromagnetic emitters (102) as per the prescribed treatment.
  • the control interface (104) allows a subject (e.g., patient) or an assistant (e.g., care giver) to start/stop treatments and to view treatment status.
  • the electromagnetic treatment device (100) may be portable so that treatment can be applied while a subject is moving around. Alternatively, the electromagnetic treatment device (100) may be fixed, allowing a subject to receive treatment when positioned correctly relative to the electromagnetic treatment device (100).
  • Electromagnetic emitters (102) may be activated one at a time by the controller (106), or several electromagnetic emitters (102) may be activated to produce electromagnetic (e.g., radio frequency) field combinations to produce controllable patterns where desired on the subject.
  • electromagnetic e.g., radio frequency
  • the electromagnetic treatment device (100) provides: 1) immunoregulatory/rebalancing actions to lower or raise brain cytokine levels to provide for reduced risk and less severe diseases of brain aging, and 2) immunoregulatory/rebalancing actions to lower or raise brain and/or body cytokine levels to provide a pathway for increasing life span/longevity. These immunoregulatory/rebalancing actions refer to levels of both pro- and anti-inflammatory cytokines being regulated/rebalanced.
  • Figure 2 is a flowchart of a method (200) for rebalancing/normalizing cytokine levels in the brain/CSF of a subject, according to an example of the principles described herein.
  • an array of electromagnetic emitters (Fig. 1 , 102) are positioned (block 201) proximal to the subject. As described above, such placement may be adjacent to a head surface or adjacent to a body surface of the subject.
  • the electromagnetic wave generator (Fig. 1 , 108) then generates (block 202) electromagnetic waves having a predetermined set of parameters (e.g., electromagnetic wave frequency, power level, pulse repetition rate).
  • the waves have a frequency between 1 megahertz (MHz) and 430 GHz (gigahertz), a power level between 0.1 and 16 watts per kilogram (W/kg) average specific absorption rate (SAR), and a pulse repetition rate between 1 and 300 hertz.
  • the method (200) also includes normalizing/rebalancing (block 203) cytokine levels in an area under the electromagnetic emitters (Fig. 1 , 102) by applying electromagnetic waves/fields to the subject through the electromagnetic emitters (Fig. 1 , 102).
  • cytokine levels are rebalanced/normalized in the brain, as indexed by cytokine levels in and around the various cellular components of the brain (referred to as brain cells) and/or in the CSF.
  • brain cells include microglia, astrocytes, choroid plexus epithelial cells, neurons.
  • a treatment session may have a specified duration of, for example, a few minutes to a few hours, or it may be continuous over days, weeks, months, or years. Any given treatment session may be repeated at predetermined intervals, for example, for multiple times a day, week, month, or even years.
  • Neurologic diseases/conditions wherein such a “pro- inflammatory” environment is present in the brain include Alzheimer’s Disease, bacterial or viral brain infections (e.g., COVID-19, Ebola, SARS, certain influenzas), Multiple Sclerosis, Amyotrophic Lateral Sclerosis (ALS), Parkinson’s Disease, cognitive impairment in and depression.
  • Alzheimer’s Disease bacterial or viral brain infections (e.g., COVID-19, Ebola, SARS, certain influenzas), Multiple Sclerosis, Amyotrophic Lateral Sclerosis (ALS), Parkinson’s Disease, cognitive impairment in and depression.
  • a smaller number of age-related neurologic diseases/conditions are characterized by an imbalance of the brain’s immune system wherein its pro- inflammatory cytokines are “hypoactive” (i.e. , low brain/CSF levels of cytokines).
  • electromagnetic field application involves an increase in brain/CSF cytokine levels.
  • diseases/conditions include Traumatic Brain Injury (TBI), stroke, AIDS, Mild Cognitive Impairment (MCI), and Alzheimer’s Disease (which can involve a hypo- or hyperactive immune system depending on its stage).
  • TBI Traumatic Brain Injury
  • MCI Mild Cognitive Impairment
  • Alzheimer’s Disease which can involve a hypo- or hyperactive immune system depending on its stage.
  • a balancing/rebalancing of anti-inflammatory cytokine levels could also be involved so that both pro- and anti-inflammatory components are in balance.
  • AD Alzheimer’s Disease
  • the disease stage involves uncontrolled brain inflammation (e.g., excess pro- inflammatory cytokines), which may be responsible for at least some of the disease progression from mild to moderate to severe stages.
  • the opposite may be the case for the prelude to AD, namely MCI.
  • the brain’s immune system is hypoactive (e.g., insufficient pro-inflammatory cytokines), with the resulting inability to resist AD pathogenesis and the ensuing conversion from MCI to AD cognitive impairment.
  • the present method (200) regulates brain/CSF cytokine levels, which may include reducing brain inflammation in AD or up-regulating cytokine levels in MCI to resist this disease.
  • Such a method (200) also is therapeutic against the neurologic diseases/conditions involving immune system imbalance/dysregulation listed above.
  • the method (200) includes using an electromagnetic treatment device (Fig. 1 , 100) employing an electromagnetic wave generator (Fig. 1 , 108), and cable-connected radiating emitters (Fig. 1 , 102) on the head to generate and radiate electromagnetic field treatment across the cranium and into the brain of a patient.
  • the electromagnetic treatment device (Fig. 1 , 100) provides in-home electromagnetic wave treatment while allowing for near complete mobility.
  • Such an electromagnetic treatment device (Fig. 1 , 100) may include a custom-printed circuit board (controller (Fig. 1 , 106)) powered by a rechargeable battery.
  • the electromagnetic treatment device (Fig. 1 , 100) employing an electromagnetic wave generator (Fig. 1 , 108), and cable-connected radiating emitters (Fig. 1 , 102) on the head to generate and radiate electromagnetic field treatment across the cranium and into the brain of a patient.
  • the electromagnetic treatment device (Fig. 1 , 100) provides in-home electromagnetic wave treatment while allowing for near complete mobility.
  • FIG. 1 , 100 in one example, provides full forebrain TEMT through a constellation of eight specialized electromagnetic emitters (Fig. 1 , 102) embedded within a doublelayered head cap.
  • these electromagnetic emitters Fig. 1 , 102 may be activated sequentially, with only one electromagnetic emitter (Fig. 1 , 102) active at any given time.
  • an electromagnetic emitter Fig.
  • electromagnetic fields are defined as consisting of electromagnetic waves received by an electromagnetic emitter (Fig. 1 , 102) that then propagates electromagnetic fields through the air and that then easily penetrate into the brain or body of the patient receiving treatment.
  • FIG. 3A shows a subject (310) wearing a TEMT device (300) called the MemorEMTM, which is an example of an electromagnetic treatment device (100) device for providing transcranial electromagnetic treatment (TEMT) to the head discussed in Figure 1.
  • Electromagnetic waves are generated with a combination control box/battery (not shown) worn on the arm.
  • a cable (314) containing wires connects this control box/battery to each of the electromagnetic emitters (e.g., Fig. 1 , 102) located within a doublelayered head cap (316).
  • the TEMT device (300) may include eight electromagnetic emitters (e.g., Fig. 1 , 102) located within a double-layered head cap (316).
  • the TEMT device (300) permits near complete mobility in-home, allowing the subject (310) to perform most home activities while receiving electromagnetic treatment.
  • the TEMT device (300) can be adjusted to several power levels, and emits no sound.
  • Figure 3B depicts the size and location of the eight electromagnetic emitters (302a-h) of a TEMT device (300).
  • the eight electromagnetic emitters (302a-h) may be enveloped between the two-layer head cap (not shown). Sequential activation of these eight electromagnetic emitters (302a-h) during any given treatment session allows for only one electromagnetic emitter (302) to be active at any given time, although simultaneous activation of several or all emitters can also be accomplished.
  • Figure 3C depicts a finite-difference time-domain (FTDT) computer simulation of the electric field generated by a single active electromagnetic emitter (Fig. 1 , 102; Fig. 3B, 302b) set at 915 MHz frequency and 4.0 W/kg Specific Absorption Rate (SAR).
  • SAR Specific Absorption Rate
  • the electromagnetic device described above provides electromagnetic treatment not only to neurons and glial cells that make up the cellular part of the brain, but also to cerebral vessels on the surface of the brain and deep cerebral vessels located within or below the cerebral cortex. That is, the area under the electromagnetic emitters (Fig. 1 , 102; Fig. 3B, 302a-h) includes the brain’s functional cells and cerebral vessels going through or on top of the brain. As such, the cellular components of blood circulating through those cerebral vessels (e.g., lymphocytes) or the vessels themselves could be affected by electromagnetic fields emanating from electromagnetic emitters (Fig. 1 , 102; Fig. 3B, 302a-h) positioned on the head’s surface.
  • the electromagnetic emitters Fig. 1 , 100; Fig 3A, 300; and Fig. 3B, 300
  • CSF cerebrospinal fluid
  • the ADAS-cog score of AD subjects is the clinical benchmark for determining their disease stage and any effects of therapeutic interventions.
  • Higher (poorer) ADAS-cog scores at baseline resulted in increased GCSF levels in CSF, while just the opposite occurred for lower (better) ADAS-cog scores.
  • This correlation demonstrates that the level of cognitive impairment is strongly associated with the direction and changes in brain/CSF cytokines induced by TEMT.
  • Such TEMT effects to increase GCSF levels in CSF of AD subjects with poorer cognitive performance are not inconsequential in view of the multiple beneficial effects that GCSF has on brain synaptogenesis, microglial activity, and neurogenesis.
  • CSF levels of GCSF were much higher than their plasma levels in all AD subjects. Therefore, it is clear that cells in the AD brain are secreting GCSF and that their secretion of GCSF is affected by TEMT administration. It is known that AD transgenic mice given three weeks of GCSF injections showed central nervous system (CNS) enhancements in hippocampal neurogenesis, microglial activation/Ap degradation, and synaptogenesis. These three beneficial effects would be anticipated to be enhanced by TEMT in those AD subjects who had low baseline GCSF levels in CSF, all of whom showed TEMT-induced increases in CSF levels of GCSF.
  • CNS central nervous system
  • TEMT may affect cytokine secretion from one or both of these CNS cell types.
  • Stimulated/activated microglia and astrocytes undergo a pro-inflammatory response by releasing inflammatory cytokines.
  • electromagnetic wave effects may be observed in both microglia and astrocytes.
  • brain microglial activation may be histologically- observed in rats following their exposure to 915 MHz radiofrequency waves.
  • microglia in cell culture given a single 20 minute electromagnetic field (EMF) exposure at 2450 MHz were activated, resulting in a pro- inflammatory secretion of TNFa.
  • 1500 MHz radiofrequency waves can inhibit proliferation of microglia in the brain.
  • Astrocytes in cell culture may be activated by exposure to 900 MHz electromagnetic waves.
  • CNS/CSF cytokine regulation by TEMT may be through affecting choriod plexus epithelium cells, which also secrete cytokines into the CSF (which the choriod plexus epithelium cells produce). As well, the release of cytokines by neurons is known to occur. Therefore, combinations of the aforementioned four brain cell types (microglial, astrocytes, choroid plexus epithelial cells, and/or neurons) may respond to TEMT by “rebalancing” multiple pro- and anti-inflammatory cytokines in the brain/CSF.
  • FIG. 8 is a flowchart of a method (800) for rebalancing or immunoregulating cytokine levels in the brain of a subject, according to an example of the principles described herein.
  • the method (800) may include positioning (block 801) an array of electromagnetic emitters (Fig. 1 , 102) proximal to a subject, generating (block 802) electromagnetic waves/fields having a predetermined set of parameters (e.g., electromagnetic wave frequency, power level, pulse repetition rate), affecting one or more of the brain’s immune-related microglia, astrocytes, choroid plexus epithelial cells, and neurons with such electromagnetic waves (block 803) to rebalance cytokine levels in the brain/CSF (804).
  • a predetermined set of parameters e.g., electromagnetic wave frequency, power level, pulse repetition rate
  • Figure 9 is a flowchart of a method (900) for rebalancing or immunoregulating cytokine levels in the brain of a subject, according to another example of the principles described herein.
  • TEMT may act through “non-immune” cells or mechanisms to rebalance cytokine levels in the brain/CSF according to the example of Figure 9.
  • the method (900) may include positioning (block 901) an array of electromagnetic emitters (Fig.
  • proximal to a subject generating (block 902) electromagnetic waves/fields having a predetermined set of parameters (e.g., electromagnetic wave frequency, power level, pulse repetition rate), affecting (block 903) one or more non-immune cells or mechanisms in the brain with such electromagnetic waves to rebalance (block 904) cytokine levels in the brain/CSF.
  • a predetermined set of parameters e.g., electromagnetic wave frequency, power level, pulse repetition rate
  • brain diseases/conditions characterized by a hypo-active brain immune system could have the “pro-inflammatory” component of this immune system re-activated (rebalanced) by TEMT.
  • MCI mild cognitive impairment
  • the reactivated and rebalanced brain immune system could prevent or resist AD pathogenesis.
  • a similar, but opposite scenario, can be envisioned for brain diseases/conditions characterized by a hyper-active brain immune system (i.e. , one with a dominant “pro-inflammatory” component).
  • TEMT or PEMT
  • TEMT may maintain the immune balance characteristic of middle age in humans.
  • the methods described herein may be performed on a “body” of a user using a peripheral electromagnetic treatment (PEMT) device employing an electromagnetic wave generator (Fig. 1 , 108), and cable-connected electromagnetic emitters (Fig. 1 , 102) to generate and radiate electromagnetic field treatment into the body of the subject beneath the electromagnetic emitter(s) (Fig. 1 , 102).
  • a peripheral electromagnetic treatment (PEMT) device employing an electromagnetic wave generator (Fig. 1 , 108), and cable-connected electromagnetic emitters (Fig. 1 , 102) to generate and radiate electromagnetic field treatment into the body of the subject beneath the electromagnetic emitter(s) (Fig. 1 , 102).
  • a subject with serious COVID-19 infection involving the brain may require multiple electromagnetic emitters (Fig. 1 , 102) positioned bilaterally on the neck, axial arm region, and lower chest in order to suppress the brain inflammation, systemic cytokine storm, and lower
  • FIG 10 illustrates an example of PEMT for addressing imbalance in brain levels of various cytokines/immune mediators via EMF applied to the body of a subject.
  • peripheral PEMT emitters 1002a-f may be used to indirectly affect brain inflammation through systemic vascular or lymphatic mechanisms or some other indirect mechanism. In any event, the effect would be to lower the high brain cytokine levels (inflammation) of the COVID-19 patient.
  • direct TEMT treatment of brain inflammation in this example would probably provide the best results, the possibility of beneficial systemic mechanisms by PEMT on brain inflammation should not be dismissed.
  • TEMT or PEMT may have far-reaching therapeutic benefits for other neurologic disorders characterized by immune system imbalance, such as Parkinson’s Disease, Lewy Body dementia, Frontotemporal lobe dementia, LATE dementia, ALS, and stroke - all of which are characterized by an imbalance of pro- vs. anti-inflammatory cytokines in either their brain/CSF or vasculature.
  • immune system imbalance such as Parkinson’s Disease, Lewy Body dementia, Frontotemporal lobe dementia, LATE dementia, ALS, and stroke - all of which are characterized by an imbalance of pro- vs. anti-inflammatory cytokines in either their brain/CSF or vasculature.
  • the following ranges of electromagnetic wave parameters being emitted may be used: a. an electromagnetic wave frequency of 1 MHz to 430 GHz b. a power level of 0.1 to 16 W/kg average Specific Absorption Rate (SAR) c. a pulse repetition rate of 1 to 300 Hz d. a duty cycle between 1 % and 100% (continuous).
  • SAR Specific Absorption Rate
  • the present specification describes a method of applying electromagnetic fields to alter brain cytokine/immune mediator levels in a subject by: 1) directly activating or suppressing cytokine/immune mediator release from brain cells having an immunologic function (e.g., microglia, astrocytes, choroid plexus epithelial cells, and neurons) through TEMT, and 2) by indirectly affecting brain cells having an immunologic function through PEMT.
  • an immunologic function e.g., microglia, astrocytes, choroid plexus epithelial cells, and neurons
  • FIG 11 is a flowchart of a method (1100) for increased lymph flow through meningeal lymphatic vessels in the brain to enhance clearance/removal of toxins from the brain, according to an example of the principles described herein.
  • the method (1100) may be utilized for removal of toxic proteins from the brain.
  • toxins such as soluble p-amyloid (Ap) and tau from the brain was via their transport through the cerebrospinal fluid (CSF) and then into the venous blood.
  • CSF cerebrospinal fluid
  • the brain has an extensive system of “meningeal” lymphatic vessels that are primarily in two brain locations: 1) on the dorsal aspect of the brain, parallel to dural venous sinuses and the middle meningeal arteries, and 2) at the base of the brain relative to the skull.
  • the brain s interstitial fluid surrounding its neurons and glial cells is drained unidirectionally into CSF, then into these meningeal lymphatic vessels as lymph, which is then transported down the neck and into cervical lymph nodes. These lymph nodes then drain the lymph into large veins to clear various toxins from the brain.
  • these meningeal lymphatic vessels and their one-way lymph flow to the venous system represents a second route (in addition to the CSF) for toxic protein clearance from the brain.
  • the meningeal lymphatics have become a target for AD therapeutics since an increase in their lymph flow would remove more toxic Ap and tau soluble aggregates (currently considered to be the root causes of AD) from the brain. Greater lymph flow in these vessels may enhance clearance of such brain toxins. Therefore, a methodology that increases flow in those lymphatic vessels (e.g., by vessel dilation) may enhance Ap and tau clearance from the brain, along with other toxins. A facilitated removal of Ap and tau from the brain would be highly desirable in view of TEMT’s primary action in the brain being to disaggregate soluble oligomers and insoluble deposits of these brain toxins, thus necessitating their enhanced clearance from the brain.
  • the method (1100) may involve positioning (block 1101) electromagnetic emitters proximal to the subject’s brain (TEMT) or body (PEMT) to generate (block 1102) electromagnetic waves having a predetermined set of parameters (e.g., electromagnetic wave frequency, power level, pulse repetition rate).
  • the resulting electromagnetic fields/waves directly or indirect induce increased flow (block 1103) through meningeal lymphatic vessels in the head to increase clearance or drainage of p-amyloid (Ap) and tau isoforms, along with other brain toxins and metabolites, from the brain (1104).
  • the enhanced removal of Ap and tau from the brain via a TEMT- induced increase in meningeal lymphatic flow could be extraordinarily important to stop or reverse AD cognitive impairment. Indeed, a dysfunction in clearance of these two toxic proteins has been hypothesized to be a major reason for why their oligomeric and insoluble forms build up in the AD brain.
  • drainage (block 1104) of Ap and tau isoforms, along with other brain toxins and metabolites, can be done by applying electromagnetic fields, through TEMT to the human head or possibly through PEMT to the human body, by electromagnetic emitters (Fig. 1 , 102) positioned on either the head or body surface, respectively. Doing so directly or indirectly increases removal of toxins (e.g., Ap, tau) from the brain via enhanced meningeal lymphatic flow/drainage.
  • toxins e.g., Ap, tau
  • FIG. 12 is a flowchart of a method (1200) for increasing human life span (longevity) via electromagnetic treatment, according to an example of the principles described herein.
  • the method (1200) includes positioning (block 1201) an array of electromagnetic emitters proximal to a subject’s head (TEMT) or body (PEMT) and generating (block 1202) electromagnetic fields/waves having a predetermined predetermined set of parameters (e.g., electromagnetic wave frequency, power level, pulse repetition rate).
  • a predetermined predetermined set of parameters e.g., electromagnetic wave frequency, power level, pulse repetition rate
  • such electromagnetic treatment may be employed at any time during human aging and for as long as desired to increase life span.
  • the electromagnetic treatment-induced increase (block 1207) in human life span could result from any number of actions/mechanisms provided by this treatment.
  • One such mechanism is the ability of treatment to balance or rebalance (block 1203) both brain and body pro- and anti-inflammatory cytokines, although other “non-immune related” actions/mechanisms of treatment (block 1204) may be involved separately or in combination.
  • actions/mechanisms of treatment result in increased life span through a reduced risk or severity of age-related diseases (block 1205) and/or through effects that are independent of age-related diseases (block 1206), such as effects on genetic background/markers, mitochondrial energy production, or antioxidant defenses.
  • Age-related diseases/conditions that TEMT and/or PEMT could reduce the occurrence and/or severity of through immune system rebalancing ( Figure 12, block 1205) and/or through effects that are independent of immune system rebalancing ( Figure 12, block 1206) include the following: all forms of dementia, all forms of cardiovascular disease, all forms of cancer of the body, AIDS, traumatic brain injury, chronic traumatic encephalopathy, postoperative cognitive dysfunction, cognitive impairment after anesthesia, Rheumatoid Arthritis, bacterial or viral infections (e.g., COVID-19, Ebola, SARS), Rheumatoid Arthritis, Multiple Sclerosis, arterial hypertension, autoimmune diseases, all forms of depression and anxiety, cognitive impairment in depression, allergy, asthma, coeliac disease, glomerulonephritis, hepatitis, inflammatory bowel disease, osteoarthritis, atherosclerosis, diabetes, COPD, chronic kidney disease, and metabolic syndrome.
  • all forms of dementia all forms of cardiovascular disease, all forms of cancer of the body,
  • Electromagnetic fields or “electromagnetic treatment” refer to interdigitated electric and magnetic waves generated by an electromagnetic wave generator, sent to an emitter and then passed into tissue as electromagnetic fields/treatment.
  • Figure 13A illustrates an example of TEMT electromagnetic waves (1301) having interdigitated electric waves (1303) and magnetic waves (1305) moving in a given direction (1307).
  • FIG. 13B illustrates an example of magnetic waves generated by magnets.
  • a magnetic coil (1311 ) generates a magnetic flux (1313), which induces a current (1315) in the brain/body (1317).
  • magnetic stimulation/treatment which involves generation of magnetic waves (e.g., magnetic flux (1313)) into a tissue by magnets, with ensuing induction of completely separate electric waves at a right angle to the magnetic waves in the tissue.
  • Such magnetic stimulation is often, but erroneously, referred to as “electromagnetic stimulation, electromagnetic waves, or Pulsed Electromagnetic Fields (PEMF’s)”.
  • PMF Pulsed Electromagnetic Fields
  • electromagnetic stimulation is a completely different neuromodulatory technology from TEMT that does not provide true electromagnetic treatment. This is amply demonstrated by looking at the units of power: electromagnetic waves of TEMT and PEMT use Watts/kg or Specific Absorption Rate (SAR), while magnetic waves use “tesla” magnetic units.
  • SAR Specific Absorption Rate

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Abstract

La présente divulgation décrit un procédé de régulation (rééquilibrage) du système immunitaire du cerveau permettant de réduire l'occurrence et/ou la gravité de maladies liées à l'âge et d'augmenter la durée de vie. Selon le procédé, un réseau d'émetteurs électromagnétiques est positionné à proximité du sujet. Un générateur d'ondes électromagnétiques génère des ondes électromagnétiques selon un ensemble prédéterminé de paramètres. Dans un exemple des émetteurs positionnés à proximité de la tête du sujet, la fonction immunitaire du cerveau est normalisée/rééquilibrée dans une zone située sous les émetteurs électromagnétiques grâce à l'application des ondes électromagnétiques au sujet par l'intermédiaire des émetteurs électromagnétiques. Avec le placement des émetteurs sur la tête ou sur le corps, un rééquilibrage des cytokines/médiateurs immunitaires du cerveau se produit, ce qui devrait se traduire par une occurrence ou une gravité moindre de maladies liées à l'âge et, par conséquent, augmenter la durée de vie humaine. En variante, un traitement électromagnétique peut augmenter la durée de vie humaine par l'intermédiaire d'un autre(d'autres) mécanisme(s) ou effet(s) qui fonctionnent indépendamment de, ou de concert avec, une occurrence/gravité réduite de maladies liées à l'âge.
PCT/US2021/056328 2021-10-22 2021-10-22 Immunorégulation du cerveau par traitement électromagnétique transcrânien WO2023069117A1 (fr)

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US20200261737A1 (en) * 2013-03-11 2020-08-20 NeuroEM Therapeutics, Inc. Immunoregulation, brain detoxification, and cognitive protection by electromagnetic treatment
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US20200261737A1 (en) * 2013-03-11 2020-08-20 NeuroEM Therapeutics, Inc. Immunoregulation, brain detoxification, and cognitive protection by electromagnetic treatment
US20200346028A1 (en) * 2014-03-11 2020-11-05 NeuroEM Therapeutics, Inc. Transcranial electromagnetic treatment

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