Method for treating disorders with photostimulation and instrument used in said method
Patent Information
- Application Number
- JP2023556646
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Priority Date
- 2022-10-27
- Filing Date
- 2022-10-27
- Publication Date
- 2025-10-31
AI Technical Summary
Current treatments for demyelinating diseases, neurodegenerative disorders, and central nervous system conditions lack effective methods for promoting myelin regeneration and oligodendrocyte survival, proliferation, and differentiation, leading to inadequate therapeutic options.
The method involves irradiating specific wavelengths of light, particularly violet light in the 350-400 nm range at blinking frequencies of 0 Hz to 70 Hz, to stimulate oligodendrocyte precursor cells and oligodendrocytes, promoting myelin regeneration and increasing myelin formation in the central nervous system, using devices with light sources and control units to administer controlled light exposure.
This approach enhances the survival, proliferation, and differentiation of oligodendrocytes, leading to improved myelin regeneration and potential treatment or prevention of demyelinating diseases, neurodegenerative disorders, tumors, and central nervous system conditions, such as multiple sclerosis, Alzheimer's disease, and spinal injuries.
Abstract
Description
Method for treating diseases using optical stimulation and device used therefor
[0001] The present invention relates to a method for treating diseases using optical stimulation and an apparatus used therefor, and more particularly to a method for treating diseases using optical stimulation in which light of a specific wavelength, such as violet light, is irradiated at a specific flashing frequency, and an apparatus used therefor.
[0002] The effects of light on the human body have been studied from various perspectives in recent years, and reports based on new findings have been published. For example, it has been reported that exposure to sunlight improves circadian rhythms (Non-Patent Document 1), that light emitted from LED lighting and liquid crystal displays using LEDs as backlights has a significant effect on the body and mind (Non-Patent Document 2), and that violet light prevents and suppresses the onset of myopia (Patent Document 1). In particular, the present inventors have recently published interesting reports on the effects of violet light on the eyes. For example, Patent Document 1 and Non-Patent Document 3 propose that light of a specific wavelength is effective in preventing and suppressing myopia, and this has generated great expectations in recent years as the number of myopic people continues to increase worldwide.
[0003] In addition, research and development of various treatment technologies is also active, particularly research and development of treatment technologies that do not use drugs or reduce the use of drugs and that reduce the burden on the body. Diseases that can be treated include, for example, demyelinating diseases, as well as neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease, and spinal cord injuries, tumors such as brain tumors (gliomas), and central nervous system diseases such as cerebral infarction.
[0004] Demyelinating diseases are diseases caused by the degeneration and loss of the myelin sheath of nerve fibers. Multiple sclerosis (MS) is an example of a demyelinating disease. MS is a chronic inflammatory disease of the central nervous system characterized by myelin damage and dysfunction of the brain, optic nerves, and spinal cord. Research and development into treatments for demyelinating diseases, including multiple sclerosis, is actively progressing, but no effective treatment has been established, and further treatment options are needed.
[0005] Oligodendrocytes are known to be associated with various diseases. For example, Non-Patent Document 4 shows that oligodendrocytes decrease with aging. Non-Patent Document 5 shows that oligodendrocytes decrease in Alzheimer's disease. Non-Patent Document 6 shows that oligodendrocyte differentiation is important for recovery from cerebral infarction. Non-Patent Document 7 shows that oligodendrocyte differentiation is important for recovery from spinal cord injury.
[0006] Fibroblast growth factor 21 (FGF21) is a pleiotropic hormone considered to be a key regulator of energy homeostasis. FGF21 is primarily secreted by the liver, but it may also be expressed in skeletal muscle. FGF21 signaling to hypothalamic glutamatergic neurons is known to be necessary for inducing reduced sugar intake and altering sweet taste preference in mice. Other studies have shown that FGF21 activates PGC-1α and enhances mitochondrial efficacy in human dopaminergic neurons, suggesting that FGF21 may play a role in dopaminergic neuron viability and PD. Peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), a key regulator of mitochondrial function and biogenesis, has been proposed as a therapeutic target for PD. Non-patent literature 8-12 disclose the function of FGF21.
[0007] Hatori Megumi, Tsubota Kazuo, Anti-Aging Medicine - Journal of the Japanese Society of Anti-Aging Medicine, Vol. 11, No. 3, 065(385)-072(392), (2015) Kazuo Tsubota, "Blue Light: A Threat to the Biological Clock", Shueisha, November 20, 2013 Hidemasa Torii et al., EBioMedicine, "DOI: http: / / dx.doi.org / 10.1016 / j.ebiom.2016.12.007". Nat Neurosci. 2018 May;21(5):683-695. Neuron. 2021 Jul 21;109(14):2292-2307.e5. Aging Dis. 2021 Dec 1;12(8):2096-2112. Front Cell Neurosci. 2021 Jan 11;14:619707. J Clin Invest. 2017 Sep 1; 127(9): 3496-3509.Cell Rep. 2022 Aug 23;40(8):111239.Nature Communications volume 13, Article number: 1897 (2022)Nature. 2010 Jun 10;465(7299):783-7.Eur J Neurosci. 2021 Jan;53(1):140-150.
[0008] WO2015 / 186723A1
[0009] The inventors have discovered that irradiation with light of a specific wavelength, particularly violet light (visible light in the 360-400 nm region) at a flickering frequency, promotes the survival, proliferation, and differentiation of oligodendrocyte precursor cells and oligodendrocytes, promotes the regeneration and increase of myelin, and activates the nervous system and the immune system. The present invention is based on this finding, and its purpose is to provide a method for treating and / or preventing diseases such as demyelinating diseases, neurodegenerative diseases, tumors, central nervous system diseases, and symptoms associated with myelination, by irradiating light of a specific wavelength, such as violet light, either at a constant light level or at a specific flickering frequency, as well as an apparatus and program for use therein.
[0010] Another object of the present invention is to provide a method for treating and / or preventing diseases such as demyelinating diseases, neurodegenerative diseases, tumors, central nervous system diseases, and conditions associated with myelination in a subject by irradiating the subject with light of a specific wavelength to promote regeneration or increase of myelin in at least one region of the subject's central nervous system, as well as an apparatus and program for use therein.
[0011] Furthermore, the present invention also aims to provide methods for promoting the regeneration or increase of myelin in at least one region of the central nervous system, and methods for promoting the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes in at least one region of the central nervous system.
[0012] In one aspect, the present disclosure relates to a method for treating and / or preventing a disease in a subject in need thereof, the method comprising irradiating the subject with light of a particular wavelength, wherein the disease is selected from the group consisting of a demyelinating disease, a neurodegenerative disease, a tumor, a central nervous system disease, and a condition associated with myelination. The method of the present disclosure comprises irradiating the subject with light of a particular wavelength to promote regeneration or increase of myelin in at least one region of the subject's central nervous system, thereby treating and / or preventing the disease in the subject, wherein the disease is selected from the group consisting of a demyelinating disease, a neurodegenerative disease, a tumor, a central nervous system disease, and a condition associated with myelination.
[0013] In one aspect, the present disclosure relates to a method for treating and / or preventing a disease in a subject in need thereof, the method comprising controlling a light irradiation device to irradiate the subject with light of a specific wavelength, thereby promoting regeneration or increase of myelin in at least one region of the subject's central nervous system, thereby treating and / or preventing the disease in the subject, wherein the disease is selected from the group consisting of a demyelinating disease, a neurodegenerative disease, a tumor, a central nervous system disease, and a condition associated with myelination. In some embodiments, the light irradiation device comprises a light source that irradiates a living body with light of a specific wavelength, either constant or at a specific flickering frequency, and a controller that controls the flickering frequency of the light source.
[0014] In the context of the present disclosure, demyelinating diseases include, but are not limited to, multiple sclerosis, neuromyelitis optica (Devic's syndrome), concentric sclerosis (Balo's disease), acute disseminated encephalomyelitis (ADEM), inflammatory diffuse sclerosis (Schilder's disease), subacute sclerotic panencephalitis (SSPE), progressive multifocal leukoencephalopathy (PML), hypoxic encephalopathy, central pontine myelinopathy, vitamin B12 deficiency, Guillain-Barré syndrome, and Binswanger's disease.
[0015] In the context of this disclosure, neurodegenerative diseases include, but are not limited to, amyotrophic lateral sclerosis (ALS), Alzheimer's disease, and spinal cord injury.
[0016] In the context of the present disclosure, tumors include, but are not limited to, brain tumors (gliomas).
[0017] In the context of the present disclosure, central nervous system diseases include, but are not limited to, cerebral infarction.
[0018] In the context of this disclosure, symptoms associated with myelination include, but are not limited to, pain, numbness, urinary incontinence, dizziness, blurred vision, and fatigue.
[0019] In one aspect, the present disclosure relates to a method for promoting regeneration or increase in myelin in at least one region of the central nervous system in a subject in need of treatment and / or prevention, the method comprising irradiating the subject with light of a particular wavelength to promote regeneration or increase in myelin in at least one region of the subject's central nervous system.
[0020] Also, in one aspect, the present disclosure relates to a method for promoting the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes in at least one region of the central nervous system in a subject in need of treatment and / or prevention, the method comprising irradiating the subject with light of a particular wavelength to promote the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes in at least one region of the central nervous system of the subject.
[0021] When applying the method according to the present disclosure, the subject may be a patient who is currently receiving or has previously received at least one drug selected from the group consisting of steroids, glatiramer acetate, fingolimod hydrochloride, mayonnaise fumarate, dimethyl fumarate, interferon beta (interferon beta-1a or interferon beta-1b), natalizumab, and ofatumumab.
[0022] The methods of the present disclosure may be applied to a patient to increase the expression of at least one gene selected from the group consisting of Sox10, Cnp, Mag, Mbp, Mobp, Myrf, Pou3f1, and Trf in at least one region of the central nervous system.
[0023] In some embodiments, the light used is violet light.
[0024] In some embodiments, the specific wavelengths used include 350-400 nm, and particularly about 380 nm.
[0025] In some embodiments, the flashing frequency used is 0 Hz or 30-70 Hz, particularly 0 Hz or 35-60 Hz, and more particularly 0 Hz or about 40 Hz.
[0026] In some embodiments, the illumination conditions further comprise the illumination time of the light source.
[0027] In some embodiments, the light source may be a pair of lighted eyeglasses or eyeglass frames, a tabletop light source, a mobile device mounted light source, a face or near-face mounted light source, a portable light source, a room light, or a desk lamp.
[0028] In some embodiments, the subject to which the methods of the present disclosure are applied is a human.
[0029] In one aspect, the present disclosure relates to an apparatus for treating and / or preventing a disease by optical stimulation, the apparatus comprising at least one light source that emits light and a drive circuit that drives the light source, wherein the light emitted by the light source is light of a specific wavelength that produces a disease treatment and / or preventive effect when irradiated onto a living body, and the disease is selected from the group consisting of a demyelinating disease, a neurodegenerative disease, a tumor, a central nervous system disease, and a condition associated with myelination.
[0030] In one aspect, the present disclosure relates to an apparatus for promoting myelin regeneration or increase through optical stimulation, comprising at least one light source that emits light and a drive circuit that drives the light source, wherein the light emitted by the light source is light of a specific wavelength that, when irradiated onto a living body, has the effect of promoting myelin regeneration or increase.
[0031] In another aspect, the present disclosure relates to an apparatus for promoting the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes through light stimulation, the apparatus comprising: at least one light source that emits light; and a drive circuit that drives the light source, wherein the light emitted by the light source is light of a specific wavelength that, when irradiated onto a living body, produces an effect of promoting the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes.
[0032] In some embodiments, the device of the present disclosure has a drive circuit that includes at least one processor communicatively connected to the light source and at least one memory, and at least one memory for storing instructions executable by the processor.
[0033] In one aspect, the present disclosure relates to a method of operating a device according to the present disclosure, the device comprising a light source that irradiates a living organism with light of a specific wavelength at a constant light level or at a specific flashing frequency, and a control unit that controls the flashing frequency of the light source, the method including a step in which the control unit controls the flashing frequency of the light source to 0 Hz or in a range of 30 to 75 Hz, and a step in which the light source irradiates the living organism with light of a wavelength in a range of 350 to 400 nm.
[0034] In one aspect, the present disclosure relates to a computer program that causes an apparatus including a light source that irradiates a living body with light of a specific wavelength at a constant light level or at a specific flashing frequency, and a control unit that controls the flashing frequency of the light source, to execute an operating method according to the present disclosure.
[0035] The method according to the present disclosure can promote the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes in a living organism exposed to light, and can promote the regeneration or increase of myelin. Promotion of the regeneration or increase of myelin can lead to the treatment and / or prevention of diseases such as demyelinating diseases, neurodegenerative diseases, tumors, central nervous system diseases, and conditions associated with myelination.
[0036] In the method and device according to the present disclosure, the light is, for example, violet light. According to this invention, a living body can be irradiated with violet light, which has a wavelength outside the visible light range, and can affect the living body without the flickering or glare that white light can cause. Violet light has a wavelength of 360 to 400 nm, which has a lower visual sensitivity than white light and is in a wavelength range that does not or is unlikely to cause discomfort to living bodies (especially humans).
[0037] In some embodiments of the present disclosure, light having a wavelength in the range of 350 to 400 nm may be used, such as light having a wavelength of 350 nm, 360 nm, 370 nm, 380 nm, 390 nm, or 400 nm, or any wavelength included in a range defined by any of the above wavelengths (e.g., the range of 370 to 390 nm). In some embodiments of the present disclosure, the wavelength includes approximately 380 nm. As used herein, the term "about" means that the value modified by the term includes values within 5% of the value.
[0038] In the method and apparatus of the present disclosure, the illumination state of the light is constant (i.e., 0 Hz) or a flashing frequency of greater than 0 Hz to 150 Hz.
[0039] In some embodiments of the present disclosure, a steady light (0 Hz) or a light with a flashing frequency in the range of 30-75 Hz may be used, for example, any of 30 Hz, 35 Hz, 40 Hz, 45 Hz, 50 Hz, 55 Hz, 60 Hz, 65 Hz, 70 Hz, or 75 Hz, or any flashing frequency within the range defined by any of the above flashing frequencies (e.g., the range of 35-45 Hz). In some embodiments of the present disclosure, the flashing frequency is about 40 Hz.
[0040] In the method and apparatus according to the present disclosure, the light is, for example, irradiance of 0.5 to 1000 μW / cm 2 or within 0.1 μW / cm 2 (0.001W / m 2 ) ~ 5000μW / cm 2 (50W / m 2 In some embodiments, oligodendrocytes can be affected by irradiation with violet light or the like within the above irradiance range. It has been confirmed that even a small amount of weak light (light with low photosensitivity) can cause characteristic phenomena.
[0041] In the method and device according to the present disclosure, the control unit of the device can change and execute the irradiation conditions, such as the irradiation state (including constant light or flashing frequency), irradiance, irradiation time, irradiation start time, irradiation end time, constant light or flashing frequency, etc., of the light by transmitting and receiving information to and from an isolated controller such as a mobile terminal. According to some embodiments, the above-mentioned various irradiation conditions are controlled in isolation, so that the irradiation conditions can be arbitrarily set to those suitable for causing oligodendrocyte regulation, thereby achieving the desired effect.
[0042] In the methods and devices disclosed herein, the light source may be a light source installed in front of or near the face, such as light-emitting glasses (see, for example, FIG. 2 ), glasses frames, a tabletop light source, a light source attached to a mobile terminal, etc. According to some embodiments, specific light can be emitted from a light source installed in front of or near the face, such as light-emitting glasses or glasses frames, which are easy to wear and comfortable to wear on a daily basis, and therefore are highly practical and can be constantly irradiated in a variety of situations and environments.
[0043] In the methods and devices disclosed herein, the light source may be a non-stationary light source, such as a portable light source, or a stationary light source, such as a room lamp, a desk lamp, or a dedicated device. According to some embodiments, the device may have various light source forms depending on the environment in which it is used. For example, the light source may be used in combination with glasses, eyeglass lenses, or contact lenses that transmit violet light. Alternatively, sunlight that has passed through glasses, eyeglass lenses, or contact lenses that transmit violet light may be used as the light source.
[0044] The light stimulation method disclosed herein is a method for controlling oligodendrocytes by irradiating a living organism (e.g., a mammal, including a human) with light of a specific wavelength at a constant light level or at a specific flashing frequency, and is characterized by controlling the emission of light that controls gene expression in the oligodendrocytes of the living organism that have received the light.
[0045] The device disclosed herein is a device for treating or preventing a disease by irradiating a living body with constant violet light, and is characterized in that it comprises a light source that emits the violet light and an emission time control unit that irradiates the violet light for a specific time or for a specific period of time, and the disease is selected from the group consisting of demyelinating diseases, neurodegenerative diseases, tumors, central nervous system diseases, and symptoms associated with myelin formation.
[0046] Furthermore, as will be described below with reference to the drawings, some embodiments of the present disclosure provide methods for treating and / or preventing the diseases in a subject in need thereof, methods for promoting myelin regeneration or increase in at least one region of the central nervous system in a subject in need thereof, methods for promoting the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes in at least one region of the central nervous system in a subject in need thereof, devices for treating and / or preventing the diseases by light stimulation, devices for promoting myelin regeneration or increase by light stimulation, devices for promoting the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes by light stimulation, methods for operating the devices, and computer programs for executing the operating methods.
[0047] FIG. 1 is an explanatory diagram of each part of the brain. It shows an example of violet light glasses that emit violet light. It is a graph showing the relationship between the spectral irradiance and wavelength of violet fluorescent light. It is the light spectrum of an LED with a peak wavelength of 375 nm. It is a block diagram of one embodiment of a biological function control device according to the present invention. It is a box plot showing genes related to myelination and oligodendrocyte differentiation among genes whose expression is upregulated by violet light (VL). WL: white light, VL: violet light. It is a diagram showing the expression pattern of oligodendrocyte differentiation marker molecules. OPC: oligodendrocyte precursor cell, pre-OL: pre-oligodendrocyte, OL: mature oligodendrocyte. It is a photograph showing MBP and DNA in the cerebral cortex obtained from an experimental mouse (VL) and a control mouse (WL). It is a diagram showing regions of the cerebral cortex obtained from an experimental mouse (VL) and a control mouse (WL). This graph compares the MBP expression region between experimental mice (VL) and control mice (WL). This graph shows the gene expression of oligodendrocyte biomarkers SOX10, CNP, MAG, MBP, Mobp, and Myrf in hippocampal tissue of the brain confirmed by quantitative PCR. This photograph shows the expression of c-Fos, MBP, CC1, and Iba1 in the nucleus accumbens of the brain. This diagram shows the location of the nucleus accumbens of the brain. This graph compares the expression of c-Fos, MBP, CC1, and Iba1 in the nucleus accumbens of the experimental group in which depression was induced (cVL) with the control group in which depression was induced (WL) and the control group in which depression was not induced (WL). This photograph shows the expression of c-Fos, MBP, CC1, and Iba1 in the prefrontal cortex of the brain. 1 shows the region of the prefrontal cortex of the brain. This graph compares the expression of c-Fos, MBP, CC1, and Iba1 in the prefrontal cortex of the brain between the experimental group in which depression was induced (cVL) and the control group in which depression was induced (WL) and the control group in which depression was not induced (WL).This graph compares FGF1 expression in the prefrontal cortex of the brain in an experimental group with induced depression (cVL) with a control group with induced depression (WL) and a control group without induced depression (WL). This graph compares FGF22 expression in the prefrontal cortex of the brain in an experimental group with induced depression (cVL) with a control group with induced depression (WL) and a control group without induced depression (WL). This graph compares FGF21 mRNA expression in the hippocampus of the left and right hemispheres of the brain in the experimental group (VL) and the control group (WL). Left indicates the left brain, and right indicates the right brain. This graph compares MAG expression (40Hz VL) in an Alzheimer's disease model animal, the P301S mutant human tau transgenic mouse (PS19), exposed to 40Hz violet light, with that in the control group (cWL).
[0048] The present disclosure provides a method for treating and / or preventing a disease in a subject in need thereof, a method for promoting myelin regeneration or increase in at least one region of the central nervous system in a subject in need thereof, a method for promoting the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes in at least one region of the central nervous system in a subject in need thereof, an apparatus for treating and / or preventing a disease using light stimulation, an apparatus for promoting myelin regeneration or increase in myelin using light stimulation, an apparatus for promoting the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes using light stimulation, a method for operating the apparatus, and a computer program for executing the method, all of which are described below with reference to the drawings. The present invention is not limited to the following embodiments and examples, and includes various modifications and applications within the spirit and scope of the present invention.
[0049] [Method for treating and / or preventing a disease] The method for treating and / or preventing a disease according to the present disclosure is characterized by comprising irradiating a subject in need of treatment and / or prevention with light of a specific wavelength.
[0050] The present inventors have discovered that irradiating a subject with light of a specific wavelength can promote the survival, proliferation, and differentiation of oligodendrocyte precursor cells and oligodendrocytes in at least one region of the subject's central nervous system, thereby activating nerves and activating the immune system. Accordingly, one aspect of the present disclosure relates to a method for promoting the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes in at least one region of the central nervous system of a subject in need of treatment and / or prevention, the method comprising irradiating the subject with light of a specific wavelength to promote the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes in at least one region of the subject's central nervous system. Here, the subject may be a living organism having oligodendrocytes, such as a mammal, particularly a human.
[0051] Oligodendrocytes, also known as oligodendrocytes, are glial cells in the central nervous system. The central nervous system consists of neurons, which transmit electrical signals and communicate information, and glial cells (neuronal glial cells), which provide nutrients to neurons and support their function. Oligodendrocytes, a type of glial cell, are particularly responsible for forming the myelin sheath that covers the axons of neurons. Oligodendrocytes undergo a series of steps—proliferation, migration, differentiation, and myelination—to ultimately myelinate the axons. Myelin acts as an insulator, accelerating the transmission of electrical signals and preventing them from leaking out of the axon and mixing with signals transmitted by other axons. Demyelinating diseases are incurable diseases of unknown cause that result in the loss of the myelin covering the nerves (demyelination), impairing nerve signal transmission, resulting in various neurological symptoms, such as numbness in the limbs. Suppressing demyelination and promoting remyelination are considered to be the key to treating demyelinating diseases. Oligodendrocytes are known to be involved in various diseases. For example, oligodendrocytes are known to decrease with aging and in Alzheimer's disease. Oligodendrocyte differentiation is known to be important for recovery from cerebral infarction and spinal cord injury.
[0052] The promotion of survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes is indicated by increased expression of at least one gene selected from the group consisting of Sox10, Cnp, Mag, Mbp, Mobp, Myrf, Pou3f1, and Trf in at least one region of the central nervous system. The at least one region of the central nervous system may be, for example, but is not limited to, the rhinencephalon, amygdala, striatum, hippocampus, cerebral neocortex, epithalamus, thalamus, hypothalamus, ventral thalamus, pituitary gland, pineal gland, third ventricle, tectum, cerebral peduncle, pretectal area, aqueduct, pons, cerebellum, medulla oblongata, or spinal cord. The present inventors have found that irradiating a subject with light of a specific wavelength increases the expression of Sox10, Cnp, Mag, Mbp, Mobp, Myrf, Pou3f1, and Trf in the subject's central nervous system, particularly the hippocampus. Thus, one aspect of the present disclosure also relates to a method for increasing the expression of at least one gene selected from the group consisting of Sox10, Cnp, Mag, Mbp, Mobp, Myrf, Pou3f1, and Trf in at least one region of the central nervous system of a subject by irradiating the subject with light of a specific wavelength. Promoting the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes leads to the promotion of myelin regeneration or increase, which in turn leads to the treatment and / or prevention of diseases such as demyelinating diseases, neurodegenerative diseases, tumors, central nervous system diseases, and conditions associated with myelination. Thus, one aspect of the present disclosure relates to a method for promoting myelin regeneration or increase in at least one region of the central nervous system in a subject in need of treatment and / or prevention, the method comprising irradiating the subject with light of a specific wavelength to promote myelin regeneration or increase in at least one region of the subject's central nervous system. Here, the subject may be a myelin-bearing organism, such as a mammal, particularly a human.
[0053] Regeneration or increase of myelin in a subject can be evaluated by visualizing myelin with MRI, for example, using a technique called myelin mapping (see, for example, Fujiyoshi et al., J Neurosci. 2016 Mar 2;36(9):2796-808). The myelin mapping technique uses MRI (3 Tesla (3T) equipment) to image myelin in approximately 10 minutes, making it easy to visualize remyelination.
[0054] As mentioned above, one aspect of the present disclosure relates to a method for treating and / or preventing a disease in a subject in need thereof, the method comprising irradiating the subject with light of a particular wavelength, wherein the disease is selected from the group consisting of a demyelinating disease, a neurodegenerative disease, a tumor, a central nervous system disease, and a condition associated with myelination, and the method may comprise irradiating the subject with light of a particular wavelength to promote regeneration or increase of myelin in at least one region of the subject's central nervous system, thereby treating and / or preventing the disease in the subject.
[0055] The demyelinating disease can be, for example, but is not limited to, any of multiple sclerosis, neuromyelitis optica (Devic's syndrome), concentric sclerosis (Balo's disease), acute disseminated encephalomyelitis (ADEM), inflammatory diffuse sclerosis (Schilder's disease), subacute sclerotic panencephalitis (SSPE), progressive multifocal leukoencephalopathy (PML), hypoxic encephalopathy, central pontine myelinopathy, vitamin B12 deficiency, Guillain-Barré syndrome, and Binswanger's disease.
[0056] Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). It is a chronic inflammatory disorder characterized by myelin damage and dysfunction of the brain, optic nerves, and spinal cord. The exact cause of MS is unknown. When MS develops, the immune system attacks the myelin sheath, resulting in demyelination, exposing axons. Demyelination disrupts nerve conduction, resulting in neurological symptoms. Primary symptoms include visual field disturbances, diplopia, sensory impairment, motor impairment, gait disturbance, urinary disturbance, dysarthria, and higher brain dysfunction. Multiple sclerosis (MS) can be broadly divided into four types: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS), and progressive relapsing MS (PRMS).
[0057] In the treatment of multiple sclerosis, high-dose intravenous pulse therapy with methylprednisolone and plasma exchange therapy are often used as acute short-term therapies. While these therapies have been shown to be effective in the short term, multiple sclerosis is a chronic disease with persistent disease activity, and therefore there is a growing need for treatments aimed at improving long-term prognosis. In addition to steroids such as methylprednisolone, available therapeutic agents include glatiramer acetate, fingolimod hydrochloride, siponimod fumarate, dimethyl fumarate, interferon beta, natalizumab, and ofatumumab. Thus, in some embodiments of the methods disclosed herein, the subject may be a patient currently receiving or who has previously received at least one drug selected from the group consisting of steroids, glatiramer acetate, fingolimod hydrochloride, siponimod fumarate, dimethyl fumarate, interferon beta, natalizumab, and ofatumumab. Therapy combining administration of these drugs with the light stimulation of the present invention may more effectively control the disease. Thus, one aspect of the present disclosure also relates to a method for treating and / or preventing a demyelinating disease in a subject in need thereof, the method comprising irradiating the subject with light of a particular wavelength and administering to the subject at least one drug selected from the group consisting of steroids, glatiramer acetate, fingolimod hydrochloride, mayonnaise fumarate, dimethyl fumarate, interferon beta, natalizumab, and ofatumumab.
[0058] The neurodegenerative disease may be, for example, but is not limited to, any of amyotrophic lateral sclerosis (ALS), Alzheimer's disease, and spinal cord injury.
[0059] The tumor may be, for example, but is not limited to, a brain tumor (glioma).
[0060] The central nervous system disease may be, for example, but is not limited to, cerebral infarction.
[0061] Symptoms associated with myelination can be, for example, but not limited to, pain, numbness, urinary incontinence, dizziness, blurred vision, and fatigue.
[0062] In some embodiments of the methods of the present disclosure, the light used may be violet light. Also, in some embodiments of the methods of the present disclosure, specific wavelengths used may include 350 to 400 nm, and particularly approximately 380 nm. The flashing frequency may be, for example, 0 Hz or 30 to 70 Hz, and particularly 0 Hz or 35 to 60 Hz. The flashing frequency may particularly be 0 Hz or approximately 40 Hz. The illumination conditions may further include the duration of illumination of the light source. The light source may be, but is not limited to, light-emitting eyeglasses or eyeglass frames, a desktop light source, a mobile terminal-mounted light source, a face-mounted or near-face light source, a portable light source, a room light, or a desk lamp.
[0063] In some embodiments of the present disclosure, the specific time for light irradiation can be any time in a range of 10 seconds to 24 hours per day, such as 10 seconds, 30 seconds, 45 seconds, 1 minute, 3 minutes, 5 minutes, 10 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 18 hours, or 24 hours, or any time within a range defined by any of the above times (e.g., a range of 1 to 12 hours). The specific period for which light irradiation continues can be, for example, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 6 months, 1 year, 2 years, 3 years, or longer.
[0064] One aspect of the present disclosure relates to a method for treating and / or preventing a disease in a subject in need thereof, the method comprising controlling a light irradiation device to irradiate the subject with light of a specific wavelength, thereby promoting regeneration or increase of myelin in at least one region of the subject's central nervous system and treating and / or preventing the disease in the subject, wherein the disease is selected from the group consisting of a demyelinating disease, a neurodegenerative disease, a tumor, a central nervous system disease, and a condition associated with myelination. In some embodiments, the light irradiation device is capable of irradiating violet light. In some embodiments, the light irradiation device is capable of irradiating light with a wavelength of 350 to 400 nm, particularly light with a wavelength of approximately 380 nm. The light irradiation device may have a flashing frequency that is controllable to, for example, 0 Hz or 30 to 70 Hz, particularly 0 Hz or 35 to 60 Hz, and the flashing frequency may be particularly 0 Hz or approximately 40 Hz. The light irradiation device may also have a controllable irradiation duration. The light source may be in the form of, but is not limited to, lighted eyeglasses or eyeglass frames, a tabletop light source, a mobile device mounted light source, a face-mounted or near-face mounted light source, a portable light source, a room light, or a desk lamp.
[0065] [Device] One aspect of the present disclosure relates to a device for treating and / or preventing a disease by light stimulation. In some embodiments, the device for treating and / or preventing a disease according to the present disclosure may include at least one light source that emits light and a drive circuit that drives the light source. Here, the light emitted by the light source is light of a specific wavelength that produces a disease treatment and / or prevention effect when irradiated onto a living body.
[0066] One aspect of the present disclosure relates to an apparatus for promoting myelin regeneration or increase through light stimulation. In some embodiments, the apparatus for promoting myelin regeneration or increase according to the present disclosure may include at least one light source that emits light and a drive circuit that drives the light source. Here, the light emitted by the light source is light of a specific wavelength that, when irradiated onto a living body, produces the effect of promoting myelin regeneration or increase.
[0067] Furthermore, one aspect of the present disclosure relates to an apparatus for promoting the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes by light stimulation. In some embodiments, the apparatus for promoting the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes according to the present disclosure may include at least one light source that emits light and a drive circuit that drives the light source. Here, the light emitted by the light source is light of a specific wavelength that, when irradiated onto a living body, produces an effect of promoting the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes.
[0068] In this specification, devices for treating and / or preventing the above-mentioned diseases using light stimulation, devices for promoting myelin regeneration or increase using light stimulation, and devices for promoting the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes using light stimulation may be collectively referred to as "biofunction control devices" or simply "devices."
[0069] These devices can stimulate oligodendrocyte precursor cells or oligodendrocytes in vivo, thereby activating nerves and activating the immune system, by controlling the light irradiation state. As described above, the expression of specific genes is enhanced in oligodendrocyte precursor cells or oligodendrocytes stimulated by light, promoting their survival, proliferation, or differentiation, thereby promoting the regeneration or increase of myelin, and further leading to the treatment and / or prevention of the aforementioned diseases.
[0070] In some embodiments, the device according to the present disclosure is a device for irradiating a living body with violet light at a constant light level or at a specific flashing frequency to control biological functions such as the survival, proliferation or differentiation of oligodendrocyte precursor cells or oligodendrocytes, myelination, etc., to activate nerves and activate the immune system, and to treat or prevent diseases, as described above. The device includes a light source that emits the violet light, a light emission cycle controller that sets the violet light to a constant light level or at a specific flashing frequency, and a light emission time controller that irradiates the violet light for a specific time or for a specific period of time, and is used to control the biological functions and treat and / or prevent diseases, wherein the diseases are selected from the group consisting of demyelinating diseases, neurodegenerative diseases, tumors, central nervous system diseases, and symptoms associated with myelination.
[0071] In addition, in some embodiments, the device according to the present disclosure is a device that controls biological functions by irradiating a living organism with constant violet light, and is characterized by comprising a light source that emits the violet light, and an emission time control unit that irradiates the violet light for a specific time or for a specific period of time.
[0072] In some embodiments, the present disclosure also relates to a device used to control biological functions through optical stimulation and treat and / or prevent diseases, the device comprising at least one light source that emits light and a drive circuit that drives the light source, wherein the light emitted by the light source is light of a specific wavelength that produces the effect when irradiated onto a living organism. Accordingly, one aspect of the present disclosure relates to a device for treating and / or preventing diseases through optical stimulation, the device comprising at least one light source that emits light and a drive circuit that drives the light source, the drive circuit including at least one processor communicatively connected to the light source and at least one memory, and at least one memory for storing instructions executable by the processor, the light source configured to emit light of a specific wavelength that produces the effect of treating and / or preventing the disease when irradiated onto a living organism. Another aspect of the present disclosure relates to an apparatus for promoting myelin regeneration or increase through photostimulation, comprising: at least one light source that emits light; and a drive circuit that drives the light source, wherein the drive circuit includes at least one processor communicatively connected to the light source and at least one memory, and at least one memory for storing processor-executable instructions, wherein the light source is configured to emit light of a specific wavelength that produces an effect of promoting myelin regeneration or increase when irradiated onto a living organism. Another aspect of the present disclosure relates to an apparatus for promoting the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes through photostimulation, comprising: at least one light source that emits light; and a drive circuit that drives the light source, wherein the drive circuit includes at least one processor communicatively connected to the light source and at least one memory, and at least one memory for storing processor-executable instructions, wherein the light source is configured to emit light of a specific wavelength that produces an effect of promoting the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes when irradiated onto a living organism.
[0073] (Light Source) The wavelength of light emitted by the light source is not particularly limited, but in some embodiments, violet light defined as 360 to 400 nm is used.
[0074] A light source with an oscillation frequency between 0 (constant light, DC light) and 150 Hz can be preferably used. The frequency can be adjusted in 0.5 Hz or 1 Hz increments by setting the control unit, making it possible to generate light with any desired flashing frequency. Increasing the flashing frequency has the advantage that the flashing becomes less noticeable, although this will vary from person to person. The flashing frequency is not limited to the 10 Hz or 60 Hz used in the experimental example.
[0075] The irradiance from the light source may be variable or constant. In some embodiments, the maximum output is 310 μW / cm. 2 For example, 0.1 μW / cm is used, but is not limited to this. 2 (0.001W / m 2 ) ~ 5000μW / cm 2 (50W / m 2 ) and those in the range of, for example, 1 μW / cm 2 (0.01W / m 2 ) ~ 1000μW / cm 2 (10W / m 2 ) and, for example, 0.5 μW / cm 2 (0.005W / m 2 ) ~ 500 μW / cm 2 (5W / m 2 ) and those in the range of 0.5 to 1000 μW / cm 2 It can be arbitrarily configured, such as within the range of 1000 to 15000. Furthermore, a light source with such irradiance can be easily applied to eyeglasses or eyeglass frames, or other portable irradiation devices, so that it can be worn in daily life. It has been confirmed that even with extremely weak light (light with low photosensitivity), characteristic phenomena occur, and it is expected that it will have an effect on various parts of the body, including the brain, and on cell activity (this term also includes gene expression control).
[0076] The light may be specified by the relative luminous efficiency. Since the features of the present invention can be realized even with a low relative luminous efficiency, it is possible to irradiate a living body with a flickering violet light that stimulates the living body, and to stimulate a desired area without burdening the living body.
[0077] The light irradiation time is preferably set arbitrarily depending on the purpose, and may be short or long. The light can be applied intermittently (at regular or irregular intervals) or continuously. The light irradiation time can be set, for example, between 8:00 AM and 1:00 PM, between 9:00 AM and 12:00 PM, or between 10:00 AM and 11:00 AM, and the period can be at least 10 minutes, at least 15 minutes, at least 20 minutes, at least 30 minutes, at least 1 hour, at least 2 hours, at least 3 hours, at least 4 hours, or 5 hours. In some embodiments, 3 hours of irradiation are applied between 9:00 AM and 12:00 PM, or 2 hours of irradiation are applied between 9:00 AM and 11:00 AM. A timer function can be used for irradiation set for such a time.
[0078] The light source may be eyeglasses or eyeglass frames with a light source. Such eyeglasses or eyeglass frames are easy to wear and comfortable to wear on a daily basis, and have a light source that emits a flashing frequency attached to them. This makes them highly practical and allows them to be worn constantly in a variety of situations and environments. The light source may be a light source installed in front of or near the face, such as a desktop light source or a light source attached to a mobile terminal, or a non-installed light source, such as a portable light source, or a installed light source, such as a room light, a desk lamp, or a dedicated device. Various light source forms can be used depending on the usage environment.
[0079] (Controller) The controller is a part that controls the illumination state of the light from the light source (constant light or flashing frequency). The controller may be equipped with a power source for supplying power to the light source, and such a power source may be a battery, or may be a power source that is connected to a battery installed in another location via a cable. Furthermore, if the controller is not movable in one place, it may be configured to be connected to a household power source or the like.
[0080] The control unit preferably changes the irradiation conditions, such as the light flashing frequency, irradiance, irradiation time, irradiation start time, irradiation end time, and flashing frequency, by transmitting and receiving information to and from an isolated controller such as a mobile terminal. Since such a control unit controls the various irradiation conditions described above in isolation, it is possible to arbitrarily set irradiation conditions suitable for causing the desired biological function control, thereby obtaining the desired effect.
[0081] Furthermore, the control unit may have a light source controller or timer function. Examples of the controller include functions to vary the frequency and irradiance, and to set the irradiation time. Examples of the timer function include a function to set the irradiance time of the light. Such a controller or timer function may be provided integrally with the device or may be a separate component.
[0082] FIG. 5 shows a simplified block diagram of an example of a device that can be used for the aforementioned biological function control, etc., as one embodiment of the device according to the present disclosure. The device shown in FIG. 5 may include various functions possessed by the devices described herein, including those for treating and / or preventing the aforementioned diseases through light stimulation, those for promoting myelin regeneration or increase through light stimulation, and those for promoting the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes through light stimulation (collectively referred to as "biological function control devices"). Accordingly, all of the devices described herein can be represented by the block diagram in FIG. 5. The biological function control device may include a light source 10 and a control unit 20. The light source 10 emits light of a specific wavelength. The wavelength of the light emitted by the light source 10 preferably includes the VL described above or 350-400 nm, more preferably 380 nm. The light source 10 may be any light source, but a light-emitting diode (LED) is preferred from the viewpoints of compactness, long life, ease of on / off control, etc. (See FIG. 3 for an example of the spectrum of a violet fluorescent lamp and FIG. 4 for an example of the spectrum of an LED). The number of light sources 10 may be one or more depending on the desired irradiation intensity and irradiation range of the light source.
[0083] The control unit 20 is connected to the light source 10 by wire or wirelessly and is configured to control the illumination conditions of the light source 10. The illumination conditions can include at least one of the blinking frequency and illumination time of the light source 10, and therefore the control unit 20 can include at least one of a blinking frequency control unit 20a and an illumination time control unit 20b. The blinking frequency can be preferably 0 Hz or 30 to 75 Hz, more preferably 0 Hz or 35 to 45 Hz, and particularly preferably 0 Hz or 40 Hz. Note that a blinking frequency of 0 Hz means constant illumination. The illumination time can be set arbitrarily, for example, within a range of 10 seconds to 24 hours per day, and the specific period of continuous illumination can also be set arbitrarily, for example, from one day to several years or longer.
[0084] The control unit 20 may include a processor such as a CPU (Central Processing Unit) and executes processing to control the irradiation conditions of the light source 10. The processing performed by the control unit 20 may be implemented by a computer program or by hardware using logic circuits. The computer program may be stored in a computer-readable recording medium. The recording medium storing the computer program may be a non-transitory recording medium. The non-transitory recording medium is not particularly limited and may be, for example, a memory card, a CD-ROM, or other recording medium. The computer program stored in the recording medium can be installed in the computer unit via an appropriate reader. Examples of the appropriate reader include a card reader if the recording medium is a memory card, and a CD drive if the recording medium is a CD-ROM. Alternatively, the computer program may be downloaded to the computer unit from an external server via a communication network.
[0085] In an apparatus according to the present disclosure, the drive circuitry may include at least one processor communicatively connected to the light source and at least one memory, and at least one memory for storing instructions executable by the processor.
[0086] 5 may be light-emitting glasses or glasses frames, a desktop light source, a mobile terminal-mounted light source, a face-mounted or nearby light source, a portable light source, a room light, or a desk lamp. The biofunction control device may also be provided as a light-emitting product, including glasses or glasses frames, a desk lamp, a mobile terminal, a mobile terminal case, a head-mounted item (such as a hat or earphone headphones), a portable light, a room light, or a desk lamp, to which at least the light source 10 out of the light source 10 and the control unit 20 is attached.
[0087] As described above, the biological function control device using optical stimulation according to the present disclosure can treat and / or prevent the above-mentioned diseases, promote the regeneration or increase of myelin, and promote the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes by irradiating a living organism with light of a specific wavelength, such as violet light, either at a constant light level or at a specific flashing frequency.
[0088] Another aspect of the present invention relates to a method for operating a biological function control device using optical stimulation. Accordingly, some embodiments of the present disclosure relate to a method for operating a device for use in controlling biological functions, the device comprising a light source that irradiates a living organism with light of a specific wavelength at constant light or a specific flashing frequency, and a control unit that controls the flashing frequency of the light source, and the device irradiates the living organism with light of the specific wavelength at constant light or the specific flashing frequency. Here, the flashing frequency of the light source may be controlled to 0 Hz or a range of 30 to 75 Hz, and the light source may irradiate the living organism with light of a wavelength in the range of 350 to 400 nm. Additionally, one aspect of the present invention relates to a computer program that causes a device comprising a light source that irradiates a living organism with light of a specific wavelength at constant light or a specific flashing frequency, and a control unit that controls the flashing frequency of the light source, to execute the above-described method.
[0089] A computer program according to the present disclosure may have instructions stored on a non-transitory computer-readable medium. When the instructions are executed by a processor, the computer program according to the present disclosure can perform predetermined steps. Thus, one aspect of the present disclosure also relates to a non-transitory computer-readable medium having instructions stored thereon, which, when executed by a processor, can cause a device including a light source that irradiates a living organism with light of a specific wavelength at a constant light level or a specific flashing frequency, and a controller that controls the flashing frequency of the light source, to operate the device by the controller to control the flashing frequency of the light source to 0 Hz or in a range of 30 to 75 Hz, and to operate the device so that the light source irradiates the living organism with light of a wavelength in the range of 350 to 400 nm.
[0090] Furthermore, one aspect of the present invention relates to an apparatus for treating and / or preventing the above-mentioned diseases by light stimulation, which may include glass, eyeglass lenses, or contact lenses that transmit violet light. Use of such an apparatus can favorably affect biological functions such as the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes, myelination, neural activation, and immune activation. Use of such an apparatus may enable the treatment and / or prevention of the above-mentioned diseases.
[0091] Example 1 (Light Exposure to Mice) Mouse cages were placed in a light exposure device (New Opto, Kanagawa, Japan) with LEDs (white: NF2W757GT-F1, purple: NSSU123, Nichia Corporation, Tokushima) attached to the top of the box. Mice in the control group were housed under white light (WL) from 8:00 AM to 8:00 PM with a 12-hour light / 12-hour dark cycle. Mice in the experimental group were also exposed to white light under the same conditions, except for exposure to violet light (VL). In the experimental group, mice were exposed to violet light from 10:00 AM to 12:00 AM every day for 16 weeks. Violet light had a wavelength of 360-400 nm (peak wavelength 375 nm) and an irradiance of 0.5-1000 μW / cm. 2 The light was irradiated within the range of 0 Hz with constant light (flash frequency of 0 Hz).
[0092] Tissue Preparation: After 16 weeks of light irradiation, 85-week-old mice were sacrificed by cervical dislocation, and whole brains were harvested from each mouse. The tissues were divided in half; one half was used for immunostaining and the other half for gene expression analysis. All tissues were snap-frozen in liquid nitrogen and stored at -80°C until analysis.
[0093] Total RNA extraction: Hippocampal tissue was homogenized with QIAzol lysis reagent (Qiagen, Germany), and total RNA was extracted using the RNeasy Mini Kit (Qiagen, Germany). The quality and quantity of all RNA samples were determined using the Nanodrop RNA Nano Kit (2100 Agilent Bioanalyzer Technologies, CA, USA). Only samples with an RNA integrity number (RIN) of >8.0 were used for gene expression analysis.
[0094] Quantitative Real-Time PCR. Total RNA was isolated from each tissue using QIAzol Lysis Reagent (Qiagen, Germany) as described above, and the concentration was measured using Nanodrop Onec (Thermo Scientific). 500 ng of total RNA was used for cDNA synthesis using a reverse transcriptase RNA kit (Applied Biosystems, Japan). Quantitative real-time PCR was performed according to a previously described protocol. Briefly, PCR reactions using SYBR Green were performed using Quant Studio 5 under the following conditions: 50°C for 2 minutes, followed by 40 cycles of 95°C for 10 seconds and 60°C for 1 minute. Values for each transcript were calculated as the average of duplicate samples across all experimental conditions. Values were normalized to GAPDH as an internal control. Data were analyzed by comparing cycle threshold values (Ct) between different groups using the 2-ΔΔCt method.
[0095] (VL-induced changes in hippocampal gene expression) To evaluate the effects of violet light (VL) exposure on brain gene expression profiles, we performed RNA-seq analysis of the hippocampus of aged mice exposed to VL. Results identified 404 differentially expressed genes (DEGs), including 231 up-regulated and 173 down-regulated genes. Gene Ontology (GO) analysis categorized DEGs into up-regulated and down-regulated genes, revealing that VL exposure increased the expression of genes involved in neural circuit formation, such as neuronal encapsulation, axonal encapsulation, and myelination. It is noteworthy that glial cell development, particularly oligodendrocyte differentiation, was included in the cluster of up-regulated genes. Thus, aged mice exposed to VL exhibited up-regulation of genes related to oligodendrocyte differentiation. Specifically, VL-upregulated genes play important roles in the differentiation of pre-oligodendrocytes (pre-OLs) into mature oligodendrocytes, including genes involved in myelin maturation, such as Sox10, Cnp, Mag, Mbp, and Mobp (Figures 6 and 7). Furthermore, VL increased the expression of Myrf, a known Sox10 cofactor that induces oligodendrocyte differentiation genes. VL also induced other oligodendrocyte-related genes, such as Pou3f1 and transferrin (Trf) (Figure 6). These data indicate that VL stimulation alters the expression of genes involved in glial differentiation, thereby promoting myelination and potentially treating or preventing demyelinating diseases.
[0096] Example 2: Brain cortex samples from 88-week-old mice exposed to violet light for 18 weeks were examined in the same manner as in Example 1. MBP (myelin basic protein), a biomarker for mature oligodendrocytes, was detected and stained with DAPI, which stains DNA. The results are shown in Figures 8 to 10. In Figure 8, VL indicates the results for the experimental group mice exposed to violet light. WL indicates the results for the control group mice not exposed to violet light. Figure 9 shows the regions of the brain cortex samples. Figure 10 is a graph comparing the MBP expression areas between the experimental and control groups. Three mice were used in the experiment, and three to four regions were examined for each mouse. In Figure 10, "Aged" indicates 88 weeks of age, and "young" indicates 13 weeks of age. Mean + SEM was calculated by one-way ANOVA with post hoc (Tukey's) analysis, with *<0.05. As shown in Figures 8 and 10, rearing mice under violet light irradiation conditions increased the area expressing MBP in the cerebral cortex, and mature oligodendrocytes increased in the cerebral cortex of aged mice. These findings suggest that the methods of the present invention can be applied to the treatment and / or prevention of neurodegenerative diseases such as Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis (ALS), and recovery from spinal cord injury. Furthermore, the methods of the present invention can be applied to the treatment and / or prevention of brain tumors (gliomas) and other conditions associated with myelination, such as pain, numbness, urinary incontinence, dizziness, decreased vision, and fatigue.
[0097] Example 3: Eight-week-old young mice were exposed to violet light for a short period of one week as in Example 1. Gene expression of oligodendrocyte biomarkers SOX10, CNP, MAG, MBP, Mobp, and Myrf was confirmed by quantitative PCR using hippocampal tissue from the brain. C57BL / 6j mice were used. The experimental group consisted of four mice, and they were exposed to violet light from 10:00 AM to 12:00 AM every day. The control group consisted of four mice, and they were housed under white light (WL) from 8:00 AM to 8:00 PM with a 12-hour light / 12-hour dark cycle. The results are shown in Figure 11. In Figure 11, VL indicates the results of the experimental group mice exposed to violet light, and WL indicates the results of the control group mice not exposed to violet light. As shown in Figure 11, the experimental mice had increased gene expression of SOX10, CNP, MAG, MBP, Mobp, and Myrf in the hippocampus tissue of the brain compared to the control mice. Thus, it was demonstrated that short-term violet light exposure is sufficient to activate and induce differentiation of oligodendrocytes in young mice. This demonstrates that the method of the present invention can be applied to the treatment and / or prevention of various central nervous system disorders and brain tumors, as well as to improving healthcare.
[0098] Example 4: Experimental animals (C57Bl6 / J) in which depression was induced using a social defeat stress model were exposed to violet light for 10 days in the same manner as in Example 1, and the expression of c-Fos, MBP, CC1, and Iba1 in the nucleus accumbens of the brain was then examined. The results are shown in Figures 12 to 14. In Figure 12, "Violet Light" indicates the results of the experimental group of mice exposed to violet light. "WL" indicates the results of the control group of mice not exposed to violet light. In Figure 12, "stress" indicates that depression was induced, and "non-stress" indicates that depression was not induced. Figure 13 shows the location of the nucleus accumbens of the brain. Figure 14 is a graph quantifying the results of the photograph in Figure 12. In Figure 14, "WL" indicates the results of the control group of mice not exposed to violet light. "cVL" indicates the results of the experimental group of mice exposed to violet light. Stress indicates whether depression was induced. As shown in Figures 12 and 14, in the experimental group of mice exposed to violet light, the mature oligodendrocyte makers CC1 and MBP were increased in the nucleus accumbens of the brain, neural activation (c-Fos) was observed, and the brain's immune cells, microglia, were increased (Iba1). This demonstrates that violet light restores oligodendrocytes, which are reduced by stress, and activates neural and immune systems. Therefore, the method of the present invention can be applied to the treatment and / or prevention of neurodegenerative diseases and tumors, and can be applied to improving healthcare.
[0099] Example 5: An experiment similar to that in Example 4 was conducted, except that the brain region was the prefrontal cortex instead of the nucleus accumbens. The results are shown in Figures 15 to 17. Figure 16 shows the prefrontal cortex region of the brain. As shown in Figures 15 and 17, in the experimental group of mice exposed to violet light, the prefrontal cortex showed increased levels of mature oligodendrocyte makers CC1 and MBP, neural activation (c-Fos), and increased levels of microglia, a brain immune cell (Iba1). These results demonstrate that violet light restores stress-induced declines in oligodendrocytes and microglia, thereby activating neural and immune systems. Therefore, the method of the present invention can be applied to the treatment and / or prevention of neurodegenerative diseases and tumors, and can be applied to improving healthcare.
[0100] Example 6: In a social defeat stress model, experimental animals (C57Bl6 / J) without induced depression and mice with induced depression were exposed to violet light for 10 days in the same manner as in Example 1. Fibroblast growth factor (FGF) gene expression was confirmed in the prefrontal cortex of the brain. FGF1 and FGF22 are known to be important factors in oligodendrocyte differentiation and myelination. The results are shown in Figures 18 and 19. In Figures 18 and 19, WL indicates the results of the control group of mice not exposed to violet light. cVL indicates the results of the experimental group of mice exposed to violet light. Stress indicates whether depression was induced by the social defeat stress model. As shown in Figures 18 and 19, 10 days of violet light exposure clearly increased gene expression of FGF1 and FGF22 in the prefrontal cortex of the brain. Since FGF1 and FGF22 are widely involved in cell proliferation, repair, inflammation suppression, and the like, it is clear that the method of the present invention can be used for a variety of purposes.
[0101] Example 7: As in Example 3, young mice (C57BL / 6j) aged 8 to 10 weeks were exposed to violet light (constant light) for 4 weeks, and FGF21 mRNA expression in the left and right hemispheres of the hippocampus was confirmed. The results are shown in Figure 20. WL indicates the control group exposed to 50 lux of white light from 8:00 to 20:00. VL indicates the experimental group exposed to 50 lux of white light from 8:00 to 20:00 and violet light from 8:00 to 11:00. The number of individuals in WL is 4, and the number of individuals in VL is 4. As shown in Figure 20, FGF21 expression was induced in the right hemisphere of the hippocampus. FGF21 is known to induce oligodendrocyte differentiation. FGF21 has also been reported to improve cognitive function in the brain. This demonstrates that the method of the present invention can be applied to induce oligodendrocyte differentiation and improve cognitive function in the brain.
[0102] Example 8 The same procedures as in Examples 1 to 7 were carried out except that instead of irradiating the violet light at a constant light (flashing frequency of 0 Hz), the violet light was irradiated at a flashing frequency of 40 Hz.
[0103] Example 9: Experiments similar to those in these Examples were conducted using an Alzheimer's disease model animal, a P301S mutant human tau transgenic mouse (PS19), except that 40 Hz violet light was used to examine the expression of the myelin-forming gene MAG (Myelin Associated Glycoprotein). The results are shown in Figure 21. In Figure 21, 40 Hz VL indicates the experimental group exposed to 40 Hz violet light, and cWL indicates the control group. As shown in Figure 21, exposure to 40 Hz violet light increased the expression of the myelin-forming gene MAG (Myelin Associated Glycoprotein). This indicates that exposure to 40 Hz violet light promotes oligodendrocyte differentiation.
[0104] All publications, applications, standards, and patents mentioned herein are incorporated by reference in their entirety, and in the event of a conflict, the present specification controls. The present invention should not be limited in scope by the specific embodiments described herein. Indeed, various modifications of the present invention in addition to those described herein will become apparent to those skilled in the art from the foregoing description and accompanying drawings. Such modifications are intended to fall within the scope of the appended claims. Some or all of the above embodiments may also be described as follows, but the disclosure of this application is not limited to the following supplementary notes.
[0105] (Appendix 1) A method for treating and / or preventing a disease in a subject in need thereof, the method comprising irradiating the subject with light of a particular wavelength, wherein the disease is selected from the group consisting of a demyelinating disease, a neurodegenerative disease, a tumor, a central nervous system disease, and a condition associated with myelination. (Appendix 2) The method of Appendix 1, the method comprising irradiating the subject with light of a particular wavelength to promote regeneration or increase of myelin in at least one region of the subject's central nervous system, thereby treating and / or preventing the disease in the subject, wherein the disease is selected from the group consisting of a demyelinating disease, a neurodegenerative disease, a tumor, a central nervous system disease, and a condition associated with myelination. (Supplementary Note 3) A method for treating and / or preventing a disease in a subject in need thereof, the method comprising controlling a light irradiation device to irradiate the subject with light of a specific wavelength, thereby promoting regeneration or increase of myelin in at least one region of the subject's central nervous system, thereby treating and / or preventing the disease in the subject, wherein the disease is selected from the group consisting of demyelinating diseases, neurodegenerative diseases, tumors, central nervous system diseases, and symptoms associated with myelination. (Supplementary Note 4) The method according to Supplementary Note 3, wherein the light irradiation device comprises a light source that irradiates a living body with light of a specific wavelength at a constant light level or at a specific flashing frequency, and a control unit that controls the flashing frequency of the light source. (Appendix 5) The method of any one of Appendices 1 to 4, wherein the demyelinating disease is selected from the group consisting of multiple sclerosis, neuromyelitis optica (Devic's syndrome), concentric sclerosis (Balo's disease), acute disseminated encephalomyelitis (ADEM), inflammatory diffuse sclerosis (Schilder's disease), subacute sclerotic panencephalitis (SSPE), progressive multifocal leukoencephalopathy (PML), hypoxic encephalopathy, central pontine myelinopathy, vitamin B12 deficiency, Guillain-Barré syndrome, and Binswanger's disease. (Appendix 6) The method of any one of Appendices 1 to 5, wherein the neurodegenerative disease is selected from the group consisting of amyotrophic lateral sclerosis (ALS), Alzheimer's disease, and spinal cord injury. (Appendix 7) The method of any one of Appendices 1 to 6, wherein the tumor is a brain tumor (glioma). (Appendix 8) The method of any one of Appendices 1 to 7, wherein the central nervous system disease is cerebral infarction.(Appendix 9) The method according to any one of Appendices 1 to 8, wherein the symptom associated with myelination is selected from the group consisting of pain, numbness, urinary incontinence, dizziness, decreased vision, and fatigue. (Appendix 10) A method for promoting myelin regeneration or increase in at least one region of the central nervous system of a subject in need of treatment and / or prevention, the method comprising irradiating the subject with light of a specific wavelength to promote myelin regeneration or increase in at least one region of the central nervous system of the subject. (Appendix 11) A method for promoting the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes in at least one region of the central nervous system of a subject in need of treatment and / or prevention, the method comprising irradiating the subject with light of a specific wavelength to promote the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes in at least one region of the central nervous system of the subject. (Appendix 12) The method of any one of Appendices 1 to 11, wherein the subject is currently receiving or has previously received at least one drug selected from the group consisting of steroids, glatiramer acetate, fingolimod hydrochloride, mayonnaise fumarate, dimethyl fumarate, interferon beta, natalizumab, and ofatumumab. (Appendix 13) The method of any one of Appendices 1 to 12, wherein the expression of at least one gene selected from the group consisting of Sox10, Cnp, Mag, Mbp, Mobp, Myrf, Pou3f1, and Trf is increased in at least one region of the central nervous system. (Appendix 14) The method of any one of Appendices 1 to 13, wherein the light is violet light. (Appendix 15) The method of any one of Appendices 1 to 14, wherein the specific wavelength comprises 350 to 400 nm. (Appendix 16) The method of Appendice 15, wherein the specific wavelength comprises about 380 nm. (Supplementary note 17) The method of any one of Supplements 1 to 16, wherein the flashing frequency is 0 Hz or 30 to 70 Hz. (Supplementary note 18) The method of Supplementary note 17, wherein the flashing frequency is 0 Hz or 35 to 60 Hz. (Supplementary note 19) The method of Supplementary note 18, wherein the flashing frequency is 0 Hz or about 40 Hz. (Supplementary note 20) The method of any one of Supplements 1 to 19, wherein the irradiation conditions further include the irradiation time of the light source.(Supplementary Note 21) The method according to any one of Supplements 1 to 20, wherein the light source is light-emitting eyeglasses or eyeglass frames, a desktop light source, a light source attached to a mobile terminal, a light source installed in front of or near the face, a portable light source, room lighting, or a desktop lamp. (Supplementary Note 22) The method according to any one of Supplements 1 to 21, wherein the subject is a human. (Supplementary Note 23) An apparatus for treating and / or preventing a disease by optical stimulation, comprising: at least one light source that emits light; and a drive circuit that drives the light source, wherein the light emitted by the light source is light of a specific wavelength that has a therapeutic and / or preventive effect on the disease when irradiated to a living body, wherein the disease is selected from the group consisting of demyelinating diseases, neurodegenerative diseases, tumors, central nervous system diseases, and symptoms associated with myelination. (Supplementary Note 24) A device for promoting myelin regeneration or increase by optical stimulation, comprising: at least one light source that emits light; and a drive circuit that drives the light source, wherein the light emitted by the light source is light of a specific wavelength that has the effect of promoting myelin regeneration or increase when irradiated to a living organism. (Supplementary Note 25) A device for promoting the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes by optical stimulation, comprising: at least one light source that emits light; and a drive circuit that drives the light source, wherein the light emitted by the light source is light of a specific wavelength that has the effect of promoting the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes when irradiated to a living organism. (Supplementary Note 26) The device according to any one of Supplementary Notes 23 to 25, wherein the drive circuit includes: at least one processor communicatively connected to the light source and at least one memory, and at least one memory for storing instructions executable by the processor. (Appendix 27) A method for operating the device described in any one of Appendices 23 to 26, wherein the device comprises a light source that irradiates a living organism with light of a specific wavelength at a constant light level or at a specific flashing frequency, and a control unit that controls the flashing frequency of the light source, the method including a step in which the control unit controls the flashing frequency of the light source to 0 Hz or in a range of 30 to 75 Hz, and a step in which the light source irradiates the living organism with light of a wavelength in a range of 350 to 400 nm.(Appendix 28) A computer program causing an apparatus including a light source that irradiates a living body with light of a specific wavelength at a constant light level or at a specific flashing frequency, and a control unit that controls the flashing frequency of the light source, to execute the operating method described in Appendix 27. (Appendix 29) A method for increasing the expression of at least one gene selected from the group consisting of Sox10, Cnp, Mag, Mbp, Mobp, Myrf, Pou3f1, and Trf in at least one region of the central nervous system of a subject by irradiating the subject with light of a specific wavelength. (Appendix 30) A method for treating and / or preventing a demyelinating disease in a subject in need thereof, the method comprising irradiating the subject with light of a specific wavelength, and administering to the subject at least one drug selected from the group consisting of steroids, glatiramer acetate, fingolimod hydrochloride, siponimod fumarate, dimethyl fumarate, interferon beta, natalizumab, and ofatumumab. (Supplementary Note 31) An apparatus for treating and / or preventing a disease by optical stimulation, comprising: at least one light source that emits light; and a drive circuit that drives the light source, wherein the drive circuit includes at least one processor communicatively connected to the light source and at least one memory, and at least one memory for storing instructions executable by the processor, wherein the light source is configured to emit light of a specific wavelength that produces a therapeutic and / or preventive effect on a disease when irradiated onto a living body, wherein the disease is selected from the group consisting of a demyelinating disease, a neurodegenerative disease, a tumor, a central nervous system disease, and a condition associated with myelination. (Supplementary Note 32) An apparatus for promoting myelin regeneration or increase through optical stimulation, comprising: at least one light source that emits light; and a drive circuit that drives the light source, wherein the drive circuit includes at least one processor communicatively connected to the light source and at least one memory, and at least one memory for storing instructions executable by the processor, and wherein the light source is configured to emit light of a specific wavelength that, when irradiated onto a living body, produces the effect of promoting myelin regeneration or increase.(Supplementary Note 33) An apparatus for promoting survival, proliferation or differentiation of oligodendrocyte precursor cells or oligodendrocytes by optical stimulation, comprising: at least one light source that emits light; and a drive circuit that drives the light source, wherein the drive circuit includes at least one processor communicatively connected to the light source and at least one memory, and at least one memory for storing instructions executable by the processor, and wherein the light source is configured to emit light of a specific wavelength that, when irradiated onto a living body, produces an effect of promoting survival, proliferation or differentiation of oligodendrocyte precursor cells or oligodendrocytes. (Supplementary Note 34) A non-transitory computer-readable medium having instructions stored thereon, which, when executed by a processor, can perform the following steps: for an apparatus comprising a light source that irradiates a living organism with light of a specific wavelength at a constant light level or at a specific flashing frequency, and a control unit that controls the flashing frequency of the light source, the control unit operating the apparatus so that the flashing frequency of the light source is controlled to 0 Hz or in a range of 30 to 75 Hz, and the light source operating the apparatus so that the light source irradiates a living organism with light of a wavelength in a range of 350 to 400 nm. (Supplementary Note 35) An apparatus for treating and / or preventing a disease by light stimulation, comprising glasses, eyeglass lenses, or contact lenses that transmit violet light, wherein the disease is selected from the group consisting of demyelinating diseases, neurodegenerative diseases, tumors, central nervous system diseases, and symptoms associated with myelination.
Claims
1. at least one light source that emits light; a drive circuit for driving the light source; and The light emitted by the light source is light of a specific wavelength that produces a disease treatment and / or prevention effect when irradiated onto a living body. A device for treating and / or preventing a disease by light stimulation, comprising: The disease is selected from the group consisting of a demyelinating disease, a neurodegenerative disease, a tumor, a central nervous system disease, and a condition associated with myelination.
2. at least one light source that emits light; a drive circuit for driving the light source; and The light emitted by the light source is light of a specific wavelength that, when irradiated to a living body, has the effect of promoting myelin regeneration or increase. A device for promoting myelin regeneration or increase through light stimulation.
3. at least one light source that emits light; a drive circuit for driving the light source; and The light emitted by the light source is light of a specific wavelength that, when irradiated onto a living body, has the effect of promoting the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes. A device for promoting the survival, proliferation, or differentiation of oligodendrocyte precursor cells or oligodendrocytes through light stimulation.
4. The drive circuit at least one processor communicatively connected to the light source and to the at least one memory; At least one memory for storing processor-executable instructions The device of any one of claims 1 to 3, comprising:
5. A method for operating the device according to any one of claims 1 to 4, wherein the device comprises a light source that irradiates a living body with light of a specific wavelength at a constant light level or at a specific flashing frequency, and a control unit that controls the flashing frequency of the light source, the method including a step in which the control unit controls the flashing frequency of the light source to 0 Hz or in a range of 30 to 75 Hz, and a step in which the light source irradiates the living body with light of a wavelength in the range of 350 to 400 nm.
6. A computer program that causes a device including a light source that irradiates a living body with light of a specific wavelength at a constant light level or at a specific flashing frequency, and a control unit that controls the flashing frequency of the light source, to execute the operating method described in claim 5.
7. 2. The device of claim 1, wherein the demyelinating disease is selected from the group consisting of multiple sclerosis, neuromyelitis optica (Devic's syndrome), concentric sclerosis (Balo's disease), acute disseminated encephalomyelitis (ADEM), inflammatory diffuse sclerosis (Schilder's disease), subacute sclerosing panencephalitis (SSPE), progressive multifocal leukoencephalopathy (PML), hypoxic encephalopathy, central pontine myelinopathy, vitamin B12 deficiency, Guillain-Barré syndrome, and Binswanger's disease.
8. 2. The device of claim 1, wherein the neurodegenerative disease is selected from the group consisting of amyotrophic lateral sclerosis (ALS), Alzheimer's disease, and spinal cord injury.
9. 2. The device of claim 1, wherein the tumor is a brain tumor (glioma).
10. 2. The method of claim 1, wherein the central nervous system disease is cerebral infarction.
11. 10. The device of claim 1, wherein the symptoms associated with myelination are selected from the group consisting of pain, numbness, urinary incontinence, dizziness, blurred vision, and fatigue.
12. The device of any one of claims 1 to 3, for a subject who is receiving or has received at least one drug selected from the group consisting of steroids, glatiramer acetate, fingolimod hydrochloride, mayonnaise fumarate, dimethyl fumarate, interferon beta, natalizumab, and ofatumumab.
13. 4. The device of any one of claims 1 to 3, wherein the device increases the expression of at least one gene selected from the group consisting of Sox10, Cnp, Mag, Mbp, Mobp, Myrf, Pou3f1 and Trf in at least one region of the central nervous system.
14. The device of any one of claims 1 to 3, wherein the light is violet light.
15. The device according to any one of claims 1 to 3, wherein the specific wavelengths are in the range of 350 to 400 nm.
16. 16. The device of claim 15, wherein the specific wavelength comprises about 380 nm.
17. 4. The device of claim 1, wherein the light source is a pair of lighted eyeglasses or eyeglass frames, a tabletop light source, a mobile terminal mounted light source, a face-mounted or near-face mounted light source, a portable light source, an indoor light, or a table lamp.