A method for treating or preventing amyotrophic lateral sclerosis (ALS) or other motor neuron disease in a subject, the method comprising administering to the subject a PKC activating compound (e.g., a bryostatin, such as bryostatin-1, or a bryolog) in a therapeutically effective amount to treat or prevent the motor neuron disease by activating PKC in the subject. The ALS may be, for example, classical ALS, primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), and progressive bulbar palsy (PBP). The PKC activating compound may be administered at an initial loading dose of about 15, 24, or 48 micrograms weekly in the first one week or consecutive two or three weeks, followed by doses of about 12, 20, or 40 micrograms alternately every two or three weeks for at least 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 24, or 30 total weeks.
A61K 38/30 - Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
2.
METHODS FOR REPAIRING NERVE DAMAGE USING PKC ACTIVATING THERAPEUTIC AGENTS
A method for treating nerve damage in a subject in need thereof, the method comprising administering to the subject a pharmaceutically effective amount of a PKC activating therapeutic agent (e.g., bryostatin compound or analogue thereof or PUFA compound or derivative thereof) on a weekly dosage regimen to result in at least partial repair or regeneration of damaged nerves in the subject, wherein the weekly dosage regimen comprises a dosage of about 10 to about 60 µg/m2 once a week for at least two weeks, wherein the at least two weeks of dosing are done consecutively or intermittently. The subject may have, for example, spinal cord injury, cochlear nerve damage, or nerve damage to direct peripheral nerves, such as in the extremities.
A method for treating nerve damage in a subject in need thereof, the method comprising administering to the subject a pharmaceutically effective amount of a PKC activating therapeutic agent (e.g., bryostatin compound or analogue thereof or PUFA compound or derivative thereof) on a weekly dosage regimen to result in at least partial repair or regeneration of damaged nerves in the subject, wherein the weekly dosage regimen comprises a dosage of about 10 to about 60 μg/m2 once a week for at least two weeks, wherein the at least two weeks of dosing are done consecutively or intermittently. The subject may have, for example, spinal cord injury, cochlear nerve damage, or nerve damage to direct peripheral nerves, such as in the extremities.
A61K 31/23 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
4.
METHODS OF TREATING AND PREVENTING NEURODEGENERATIVE DISEASES WITH HGF ACTIVATING COMPOUNDS
A method for treating or preventing a neurodegenerative disease in a subject, the method comprising administering an HGF activating compound in a therapeutically effective amount to treat or prevent the neurodegenerative disease by activating HGF in the subject. The neurodegenerative disease may be, for example, Alzheimer's Disease, Parkinson's Disease, multiple sclerosis, dementia, or mild cognitive impairment. The methods may also be more generally directed to improving or enhancing cognitive ability, preventing or treating cognitive impairment, preventing or treating a neurodegenerative disease or condition, and/or preventing or treating a disease or condition associated with neuronal or synaptic loss according to the disclosed regimens.
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/215 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
A61K 31/357 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
5.
TREATMENT OF MULTIPLE SCLEROSIS USING PKC ACTIVATORS
A method for treating or preventing mild, moderate, or advanced multiple sclerosis (MS) in a subject, the method comprising administering to the subject a PKC activating compound (e.g., a bryostatin, such as bryostatin-1, or a bryolog) in a therapeutically effective amount to result in mitigation or prevention of demyelination, initiation of remyelination, or reduction or prevention of neuroinflammation in early MS. The MS may be, for example, relapsing-remitting MS (RRMS), primary-progressive MS (PPMS), secondary-progressive MS (SPMS), or progressive-relapsing MS (PRMS). The PKC activating compound may be administered at an initial loading dose of about 15, 24, or 48 micrograms weekly in the first one week or consecutive two or three weeks, followed by doses of about 12, 20, or 40 micrograms alternately every two or three weeks for at least 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 24, or 30 total weeks.
A method for treating or preventing optic nerve inflammation or other neurological inflammation or associated disorder (e.g., early MS) in a subject, the method comprising administering to the subject a PKC activating compound (e.g., a bryostatin, such as bryostatin-1, or a bryolog) in a therapeutically effective amount to treat or prevent the neurological inflammation by activating PKC in the subject. The optic nerve inflammation may be, for example, optic neuritis, neuromyelitis optica, or diabetic papillopathy, any of which may be acute, subacute, or nascent. The PKC activating compound may be administered at an initial loading dose of about 15, 24, or 48 micrograms weekly in the first one week or consecutive two or three weeks, followed by doses of about 12, 20, or 40 micrograms alternately every two or three weeks for at least 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 24, or 30 total weeks.
The present invention relates to methods of activate an isoform of protein kinase C (PKC) for the treatment of neurological diseases including Alzheimers disease and stroke using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids. The present invention also relates to methods of reducing neurodegeneration using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids.
C07D 303/42 - Acyclic compounds having a chain of seven or more carbon atoms, e.g. epoxidised fats
A61K 31/045 - Hydroxy compounds, e.g. alcoholsSalts thereof, e.g. alcoholates
A61K 31/23 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
A61K 31/231 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having one or two double bonds
A61K 31/335 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
A61P 25/00 - Drugs for disorders of the nervous system
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61K 31/201 - Carboxylic acids, e.g. valproic acid having a carboxyl group bound to an acyclic chain of seven or more carbon atoms, e.g. stearic, palmitic or arachidic acid having one or two double bonds, e.g. oleic or linoleic acid
C07C 53/134 - Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen containing rings monocyclic
C07C 69/608 - Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a ring other than a six-membered aromatic ring in the acid moiety
C07D 303/40 - Compounds containing oxirane rings with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals by ester radicals
A method for treating or preventing long COVID in a subject who has contracted or is at risk of contracting COVID, the method comprising administering to said subject a pharmaceutically effective amount of a PKC activator (e.g., bryostatin, bryolog, PUFA, cyclopropanated PUFA, epoxidized PUFA, growth factor, or growth factor activating compound) before or during initial contraction of COVID, wherein the subject may have contracted COVID or exhibited the first symptoms of COVID at least one month before administering the PKC activator to the subject. In some cases, the subject may be afflicted with long COVID and exhibits at least one symptom of long COVID selected from intermittent fatigue, lack of energy, respiratory problems, chest pain, joint pain, muscle pain or soreness, vascular problems, neurological problems, and/or skin conditions.
G16H 50/80 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for detecting, monitoring or modelling epidemics or pandemics, e.g. flu
9.
METHOD OF INDUCING SYNAPTOGENESIS BY ADMINISTERING ANGIOTENSIN AND ANALOGUES THEREOF
A method for inducing synaptogenesis in a subject having a neurodegenerative disease, the method comprising administering an angiotensin or analogue thereof in a therapeutically effective amount to induce synaptogenesis in said subject. The neurodegenerative disease may be, for example, Alzheimer's Disease, Parkinson's Disease, multiple sclerosis, dementia, or mild cognitive impairment. The methods may also be generally directed to improving or enhancing cognitive ability, preventing or treating cognitive impairment, preventing or treating a neurodegenerative disease or condition, and/or preventing or treating a disease or condition associated with neuronal or synaptic loss according to the disclosed regimens.
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
10.
METHOD OF INDUCING SYNAPTOGENESIS BY ADMINISTERING ANGIOTENSIN AND ANALOGUES THEREOF
A method for inducing synaptogenesis in a subject having a neurodegenerative disease, the method comprising administering an angiotensin or analogue thereof in a therapeutically effective amount to induce synaptogenesis in said subject. The neurodegenerative disease may be, for example, Alzheimer's Disease, Parkinson's Disease, multiple sclerosis, dementia, or mild cognitive impairment. The methods may also be generally directed to improving or enhancing cognitive ability, preventing or treating cognitive impairment, preventing or treating a neurodegenerative disease or condition, and/or preventing or treating a disease or condition associated with neuronal or synaptic loss according to the disclosed regimens.
A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61P 43/00 - Drugs for specific purposes, not provided for in groups
11.
PKC-activating compounds for the treatment of neurodegenerative diseases
The present invention relates to methods of activate an isoform of protein kinase C (PKC) for the treatment of neurological diseases including Alzheimer's disease and stroke using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids. The present invention also relates to methods of reducing neurodegeneration using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids.
C07D 303/42 - Acyclic compounds having a chain of seven or more carbon atoms, e.g. epoxidised fats
A61K 31/045 - Hydroxy compounds, e.g. alcoholsSalts thereof, e.g. alcoholates
A61K 31/23 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
A61K 31/231 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having one or two double bonds
A61K 31/335 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
A61P 25/00 - Drugs for disorders of the nervous system
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61K 31/201 - Carboxylic acids, e.g. valproic acid having a carboxyl group bound to an acyclic chain of seven or more carbon atoms, e.g. stearic, palmitic or arachidic acid having one or two double bonds, e.g. oleic or linoleic acid
C07C 53/134 - Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen containing rings monocyclic
C07C 69/608 - Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a ring other than a six-membered aromatic ring in the acid moiety
C07D 303/40 - Compounds containing oxirane rings with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals by ester radicals
A method for treating or preventing mild, moderate, or advanced multiple sclerosis (MS) in a subject, the method comprising administering to the subject a PKC activating compound (e.g., a bryostatin, such as bryostatin-1, or a bryolog) in a therapeutically effective amount to result in mitigation or prevention of demyelination, initiation of remyelination, or reduction or prevention of neuroinflammation in early MS. The MS may be, for example, relapsing-remitting MS (RRMS), primary-progressive MS (PPMS), secondary-progressive MS (SPMS), or progressive-relapsing MS (PRMS). The PKC activating compound may be administered at an initial loading dose of about 15, 24, or 48 micrograms weekly in the first one week or consecutive two or three weeks, followed by doses of about 12, 20, or 40 micrograms alternately every two or three weeks for at least 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 24, or 30 total weeks.
A method for treating or preventing optic nerve inflammation or other neurological inflammation or associated disorder (e.g., early MS) in a subject, the method comprising administering to the subject a PKC activating compound (e.g., a bryostatin, such as bryostatin-1, or a bryolog) in a therapeutically effective amount to treat or prevent the neurological inflammation by activating PKC in the subject. The optic nerve inflammation may be, for example, optic neuritis, neuromyelitis optica, or diabetic papillopathy, any of which may be acute, subacute, or nascent. The PKC activating compound may be administered at an initial loading dose of about 15, 24, or 48 micrograms weekly in the first one week or consecutive two or three weeks, followed by doses of about 12, 20, or 40 micrograms alternately every two or three weeks for at least 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 24, or 30 total weeks.
A method for treating or preventing amyotrophic lateral sclerosis (ALS) or other motor neuron disease in a subject, the method comprising administering to the subject a PKC activating compound (e.g., a bryostatin, such as bryostatin-1, or a bryolog) in a therapeutically effective amount to treat or prevent the motor neuron disease by activating PKC in the subject. The ALS may be, for example, classical ALS, primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), and progressive bulbar palsy (PBP). The PKC activating compound may be administered at an initial loading dose of about 15, 24, or 48 micrograms weekly in the first one week or consecutive two or three weeks, followed by doses of about 12, 20, or 40 micrograms alternately every two or three weeks for at least 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 24, or 30 total weeks.
A method for treating or preventing amyotrophic lateral sclerosis (ALS) or other motor neuron disease in a subject, the method comprising administering to the subject a PKC activating compound (e.g., a bryostatin, such as bryostatin-1, or a bryolog) in a therapeutically effective amount to treat or prevent the motor neuron disease by activating PKC in the subject. The ALS may be, for example, classical ALS, primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), and progressive bulbar palsy (PBP). The PKC activating compound may be administered at an initial loading dose of about 15, 24, or 48 micrograms weekly in the first one week or consecutive two or three weeks, followed by doses of about 12, 20, or 40 micrograms alternately every two or three weeks for at least 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 24, or 30 total weeks.
A61K 38/30 - Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61K 9/00 - Medicinal preparations characterised by special physical form
The present disclosure describes novel PKC-ε activators chosen from halogenated esters of unsaturated fatty acids and derivatives thereof, including halogenated esters of both polyunsaturated and monounsaturated fatty acids and derivatives thereof. The disclosure further relates to compositions, kits, and methods for treatment using the halogenated esters.
C07C 69/635 - Halogen-containing esters of saturated acids containing rings in the acid moiety
A61K 31/202 - Carboxylic acids, e.g. valproic acid having a carboxyl group bound to an acyclic chain of seven or more carbon atoms, e.g. stearic, palmitic or arachidic acid having three or more double bonds, e.g. linolenic acid
A61K 31/23 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
A61K 31/336 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having three-membered rings, e.g. oxirane, fumagillin
A61P 7/00 - Drugs for disorders of the blood or the extracellular fluid
17.
METHODS OF TREATING AND PREVENTING NEURODEGENERATIVE DISEASES WITH HGF ACTIVATING COMPOUNDS
A method for treating or preventing a neurodegenerative disease in a subject, the method comprising administering an HGF activating compound in a therapeutically effective amount to treat or prevent the neurodegenerative disease by activating HGF in the subject. The neurodegenerative disease may be, for example, Alzheimer's Disease, Parkinson's Disease, multiple sclerosis, dementia, or mild cognitive impairment. The methods may also be more generally directed to improving or enhancing cognitive ability, preventing or treating cognitive impairment, preventing or treating a neurodegenerative disease or condition, and/or preventing or treating a disease or condition associated with neuronal or synaptic loss according to the disclosed regimens.
A61K 31/357 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
A61K 31/215 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
A61K 9/00 - Medicinal preparations characterised by special physical form
18.
METHODS OF TREATING AND PREVENTING NEURODEGENERATIVE DISEASES WITH HGF ACTIVATING COMPOUNDS
A method for treating or preventing a neurodegenerative disease in a subject, the method comprising administering an HGF activating compound in a therapeutically effective amount to treat or prevent the neurodegenerative disease by activating HGF in the subject. The neurodegenerative disease may be, for example, Alzheimer's Disease, Parkinson's Disease, multiple sclerosis, dementia, or mild cognitive impairment. The methods may also be more generally directed to improving or enhancing cognitive ability, preventing or treating cognitive impairment, preventing or treating a neurodegenerative disease or condition, and/or preventing or treating a disease or condition associated with neuronal or synaptic loss according to the disclosed regimens.
Dosing regimens and methods are disclosed for upregulating protein kinase C (PKC) while reducing subsequent downregulation, comprising administering a PKC activator once a week for three consecutive weeks followed by cessation of administration or dosing for three consecutive weeks. Also described are methods for improving or enhancing cognitive ability, preventing or treating cognitive impairment, preventing or treating a neurodegenerative disease or condition, and/or preventing or treating a disease or condition associated with neuronal or synaptic loss according to the disclosed regimens.
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61K 9/00 - Medicinal preparations characterised by special physical form
A61P 25/26 - Psychostimulants, e.g. nicotine, cocaine
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
20.
PKC-activating compounds for the treatment of neurodegenerative diseases
The present invention relates to methods of activate an isoform of protein kinase C (PKC) for the treatment of neurological diseases including Alzheimer's disease and stroke using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids. The present invention also relates to methods of reducing neurodegeneration using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids.
C07D 303/42 - Acyclic compounds having a chain of seven or more carbon atoms, e.g. epoxidised fats
A61K 31/045 - Hydroxy compounds, e.g. alcoholsSalts thereof, e.g. alcoholates
A61K 31/23 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
A61K 31/231 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having one or two double bonds
A61K 31/335 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
A61P 25/00 - Drugs for disorders of the nervous system
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61K 31/201 - Carboxylic acids, e.g. valproic acid having a carboxyl group bound to an acyclic chain of seven or more carbon atoms, e.g. stearic, palmitic or arachidic acid having one or two double bonds, e.g. oleic or linoleic acid
C07C 53/134 - Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen containing rings monocyclic
C07C 69/608 - Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a ring other than a six-membered aromatic ring in the acid moiety
C07D 303/40 - Compounds containing oxirane rings with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals by ester radicals
A method for treating Alzheimer's disease (AD) by administering to an AD patient a PKC activator, such as a bryostatin-1, without administering a NMDA receptor antagonist, such as memantine.
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61K 9/00 - Medicinal preparations characterised by special physical form
The present disclosure describes novel PKC-ε activators chosen from halogenated esters of unsaturated fatty acids and derivatives thereof, including halogenated esters of both polyunsaturated and monounsaturated fatty acids and derivatives thereof. The disclosure further relates to compositions, kits, and methods for treatment using the halogenated esters.
A61K 31/23 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
A61K 31/202 - Carboxylic acids, e.g. valproic acid having a carboxyl group bound to an acyclic chain of seven or more carbon atoms, e.g. stearic, palmitic or arachidic acid having three or more double bonds, e.g. linolenic acid
A61K 31/336 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having three-membered rings, e.g. oxirane, fumagillin
A61P 7/00 - Drugs for disorders of the blood or the extracellular fluid
C07C 69/635 - Halogen-containing esters of saturated acids containing rings in the acid moiety
patents
