The disclosure provides methods of inducing ketosis in a non-human mammal in need thereof, comprising administering to the non-human mammal an effective amount of a compound of Formula I, wherein the amount is from 125 mg/kg to 500 mg/kg.
A61K 9/00 - Medicinal preparations characterised by special physical form
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
NNNN-PPG, and chemical analogs thereof, as well-tolerated suicide inhibitors of HYPDH/PRODH2 and/or PRODH1 provide evaluation of their efficacy as new therapeutic agents. Provided are compositions, methods of treating, and methods of targeting PRODH2, PRODH1, or a combination thereof.
C07C 69/675 - Esters of carboxylic acids having esterified carboxyl groups bound to acyclic carbon atoms and having any of the groups OH, O-metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids of saturated hydroxy-carboxylic acids
inter aliainter alia, are C-terminal KIBRA peptides that are useful for treating tau-associated memory deficit disorders. Also provided are C-terminal KIBRA peptides that are useful for treating aging-associated cognitive decline.
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
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
5.
FORMULATIONS FOR EXTENDING LIFESPAN AND HEALTHSPAN
Described herein are compositions for delaying onset or delaying progression of frailty, reversing aging phenotype, extending healthspan, compressing morbidity, increasing lifespan and reducing formation of senescent cells.
Methods are provided that relate to the discovery that dihomo-gamma linolenic acid (DGLA) is a potent senolytic agent. Accordingly, in certain embodiments, methods of selectively killing one or more senescent cells in a subject in need thereof are provided wherein the method(s) involves administering to the subject an effective amount of DGLA.
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 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
7.
SYNERGISTIC MODULATORS OF ALPHA-DICARBONYL DETOXIFICATION AND THEIR USE FOR INDUCING WEIGHT LOSS AND THE TREATMENT OF DIABETIC PATHOLOGIES
In various embodiments compositions and methods are provided for inducing or increasing weight loss or reducing or preventing weight gain in a mammal. In certain embodiments the methods comprise administering to the mammal a combination of at least two agents selected from the group consisting of lipoic acid and/or a lipoic acid analog, nicotinamide and/or a nicotinamide analog, thiamine and/or a thiamine analog, piperine and/or a piperine analog, pyridoxamine and/or a pyridoxamine analog. In certain embodiments the combination of agents provides a synergistic effect.
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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
8.
USE OF EXOGENOUS KETONE ESTERS TO INDUCE WEIGHT LOSS IN MAMMALS
In various embodiments method and compositions are provided for inducing weight loss in a mammal. In certain embodiments the methods involve administering to a mammal an effective amount of a fatty acid β-hydroxyester compounds and/or one or more esters of butanediol.
Provided herein are methods and compositions for an epigenetic clock comprising differentiation-independent methylation sites to asses biological age of a human subject.
Mayo Foundation for Medical Education and Research (USA)
Unity Biotechnology, Inc. (USA)
Inventor
Laberge, Remi-Martin
Campisi, Judith
Demaria, Marco
Childs, Bennett G.
Van Deursen, Jan M. A.
David, Nathaniel
Vasserot, Alain Philippe
Abstract
This invention establishes a new paradigm for treatment of Parkinson's disease (PD) by eliminating senescent cells that reside in or around the site of the disease pathophysiology. Exposure of test subjects to the herbicide paraquat (PQ) increases the risk for developing Parkinson's disease. The data in this disclosure show that PQ induces a senescence arrest and SASP in astrocytes, in culture and in vivo in mice, and senescent cell markers were present in astrocytes in midbrain tissue from PD patients. In a transgenic mouse model, senescent cell ablation protected against PQ-induced PD-like neuropathology. Removal of senescent cells from affected sites using small molecule agents that specifically target senescent cells can help prevent or ameliorate signs and symptoms of the disease.
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
A61K 31/428 - Thiazoles condensed with carbocyclic rings
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 47/36 - Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 11/00 - Drugs for disorders of the respiratory system
In some embodiments, a smart cell drug delivery (SmaCD) system is provided. The SmaCD system can comprise an engineered mammalian regulatory immune cell comprising: (a) a chimeric antigen receptor (CAR) comprising a first binding domain that specifically binds a target antigen associated to central nervous system (CNS) pathologies and or CNS mammalian cells, a transmembrane domain, and a cytoplasmic domain comprising none, one, two, or more costimulatory domains, and an intracellular signaling domain capable of modulating endogenous signaling; or (b) a nucleic acid sequence encoding a DNA binding sequence, a promoter sequence, and a polynucleotide encoding a therapeutic payload, wherein the therapeutic payload comprises at least one therapeutic protein or at least one therapeutic nucleic acid; and a modular synthetic receptor comprising: an extracellular domain comprising a second binding domain that specifically binds a target antigen, a regulatory region; and an intracellular domain comprising a transcriptional activator, wherein binding of the second binding domain to the target antigen causes release of the intracellular domain, binding of the transcriptional activator to the DNA binding sequence and activating expression of the therapeutic payload; or (a) and (b).
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
C12N 5/078 - Cells from blood or from the immune system
C12N 15/62 - DNA sequences coding for fusion proteins
C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
C12Q 1/6897 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids involving reporter genes operably linked to promoters
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
12.
SUPPRESSORS OF SITE IQ ELECTRON LEAK AND USES THEREOF
Described herein, inter alia, are suppressors of site IQ electron leak (SIQELs) and uses thereof. Further disclosed pharmaceutical compositions comprising the compounds and method of treating or preventing an age-related disorder in a subject, comprising administering to the subject a therapeutically effective amount of the compounds.
A61K 31/167 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen atom of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
A61K 31/428 - Thiazoles condensed with carbocyclic rings
In certain embodiments APP-specific BACE inhibitors (ASBIs) are provided as well as uses thereof. In certain embodiments methods of preventing or delaying the onset of a pre-Alzheimer's condition and/or cognitive dysfunction, and/or ameliorating one or more symptoms of a pre-Alzheimer's condition and/or cognitive dysfunction, or preventing or delaying the progression of a pre-Alzheimer's condition or cognitive dysfunction to Alzheimer's disease are provided where the method involves administering to a subject in need thereof an APP specific BACE inhibitor (ASBI) in an amount sufficient to prevent or delay the onset of a pre-Alzheimer's cognitive dysfunction, and/or to ameliorate one or more symptoms of a pre-Alzheimer's cognitive dysfunction, and/or to prevent or delay the progression of a pre-Alzheimer's cognitive dysfunction to Alzheimer's disease. In certain embodiments the ASBI is a flavonoid (e.g. galangin) or flavonoid prodrug (e.g., galangin prodrug).
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
A61K 31/352 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. cannabinols, methantheline
A61K 31/366 - Lactones having six-membered rings, e.g. delta-lactones
C07D 311/24 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
C07D 311/30 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
14.
N-PROPARGYLGLYCINE: A UNIQUE INHIBITOR OF PROLINE DEHYDROGENASE WITH BRAIN-ENHANCING MITOHORMESIS PROPERTIES CAPABLE OF MITIGATING THE PATHOGENESIS OF NEURODEGENERATIVE DISORDERS
In certain embodiments, methods of activating the mitochondrial unfolded protein response (UPRmt) and inducing mitohormesis in the brain and/or central nervous system of a mammal are provided where the methods can involve administering to the mammal an effective amount of N-proparglyglycine (N-PPG). In certain embodiments, the mammal is a mammal with a neurodegenerative disease and the method provides for the treatment or prophylaxis of the neurodegenerative disease.
A61K 31/197 - Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid (GABA), beta-alanine, epsilon-aminocaproic acid, pantothenic acid
A61K 9/00 - Medicinal preparations characterised by special physical form
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
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
Described herein are compositions for delaying onset or delaying progression of frailty, reversing aging phenotype, extending healthspan, compressing morbidity, increasing lifespan and reducing formation of senescent cells.
A61K 31/575 - Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
A61K 31/593 - 9,10-Secocholestane derivatives, e.g. cholecalciferol, vitamin D3
C12Q 1/60 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving cholesterol
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C07J 9/00 - Normal steroids containing carbon, hydrogen, halogen, or oxygen, substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
20.
METHODS OF INDUCING AUTOPHAGY USING COUMARIN DERIVATIVES AND RELATED COMPOUNDS
In various embodiments compounds that induce and/or promote autophagy are provided as wells as methods of use thereof (e.g., in the prophylaxis or treatment of chronic pathologies associated with aging). In one illustrative, but non-limiting embodiments the compound(s) comprise, inter alia, coumarin 106.
A61K 31/4745 - Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
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 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
21.
p16INK4a INHIBITOR FOR PREVENTING OR TREATING HUNTINGTON'S DISEASE
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (France)
ASSISTANCE PUBLIQUE HOPITAUX DE PARIS (France)
BUCK INSTITUTE FOR RESEARCH ON AGING (USA)
Inventor
Neri, Christian
Farina, Francesca
Voisin, Jessica
Ellerby, Lisa
Abstract
A p16INK4a inhibitor, a composition that includes the p16INK4a inhibitor, or a pharmaceutical composition that includes the p16INK4a inhibitor, for use in the prevention and/or the treatment of Huntington's disease, wherein the p16INK4a inhibitor is a nucleic acid or a peptide, a small compound molecule or a marketed drug.
In various embodiments method and compositions are provided for inducing weight loss in a mammal. In certain embodiments the methods involve administering to a mammal an effective amount of a fatty acid ?-hydroxyester compounds and/or one or more esters of butanediol.
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 31/22 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
Methods and compositions are provided herein that pertain to the discovery that the crystallin alpha B (CRYAB) gene and gene product provides an effective target for senolytic agents. In certain embodiments, methods of selectively killing one or more senescent cells in a subject in need thereof are provided wherein the method involves administering to the subject an effective amount of an agent that inhibits expression and/or aggregation of a CRYAB protein.
A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
A61K 31/575 - Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
A61K 31/593 - 9,10-Secocholestane derivatives, e.g. cholecalciferol, vitamin D3
24.
Methods and Compositions for Altering Senescence Associated Secretory Phenotype
Disclosed herein are methods and compositions comprising alpha ketoglutarate (AKG) for altering senescence-associated secretory phenotype (SASP), and related diseases.
In various embodiments method and compositions are provided for inducing weight loss in a mammal. In certain embodiments the methods involve administering to a mammal an effective amount of a fatty acid β-hydroxyester compounds and/or one or more esters of butanediol.
The present invention provides a method of detecting senescent cells or diagnosing cellular senescence in a subject wherein the level of one or more selected miRNAs is quantified in a sample from said subject.
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
In various embodiments compositions and methods are provided for inducing or increasing weight loss or reducing or preventing weight gain in a mammal. In certain embodiments the methods comprise administering to the mammal a combination of at least two agents selected from the group consisting of lipoic acid and/or a lipoic acid analog, nicotinamide and/or a nicotinamide analog, thiamine and/or a thiamine analog, piperine and/or a piperine analog, pyridoxamine and/or a pyridoxamine analog. In certain embodiments the combination of agents provides a synergistic effect.
A61K 31/7084 - Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
28.
N-PROPARGYLGLYCINE: A UNIQUE INHIBITOR OF PROLINE DEHYDROGENASE WITH BRAIN-ENHANCING MITOHORMESIS PROPERTIES CAPABLE OF MITIGATING NEURODEGENERATIVE DISORDERS
In certain embodiments, methods of activating the mitochondrial unfolded protein response (UPRmt) and inducing mitohormesis in the brain and/or central nervous system of a mammal are provided where the methods can involve administering to the mammal an effective amount of N-proparglyglycine (N-PPG). In certain embodiments, the mammal is a mammal with a neurodegenerative disease and the method provides for the treatment or prophylaxis of the neurodegenerative disease.
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 25/00 - Drugs for disorders of the nervous system
A61K 31/4427 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
C07D 213/02 - Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
C07D 213/04 - Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
A61K 31/41 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which is nitrogen, e.g. tetrazole
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
In various embodiments methods for the treatment or prophylaxis of an age-related and/or pathology-associated increase in intestinal barrier permeability are provided. In certain embodiments the methods comprise administering to a mammal in need thereof an effective amount of one or more agent(s) that inhibit superoxide or hydrogen peroxide production from the outer ubiquinone-binding site of complex III of the mitochondrial electron transport chain (site IIIQo).
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/343 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
A61K 31/4365 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
Methods are provided that relate to the discovery that dihomo-gamma linolenic acid (DGLA) is a potent senolytic agent. Accordingly, in certain embodiments, methods of selectively killing one or more senescent cells in a subject in need thereof are provided wherein the method(s) involves administering to the subject an effective amount of DGLA.
A61K 8/30 - Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
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
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
Methods are provided that relate to the discovery that dihomo-gamma linolenic acid (DGLA) is a potent senolytic agent. Accordingly, in certain embodiments, methods of selectively killing one or more senescent cells in a subject in need thereof are provided wherein the method(s) involves administering to the subject an effective amount of DGLA.
A61K 8/30 - Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
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
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
In various embodiments methods of utilizing gene drive constructs in asexual organisms such as viruses are provided. In certain embodiments the methods involve transfecting or infecting a cell with a modified DNA vims containing a gene drive construct; and infecting the cell with the target vims where the genome of said target DNA virus is modified by insertion of the gene drive construct into the genome of the target DNA virus and a population of modified target viruses (containing the gene drive construct) is produced.
Mayo Foundation for Medical Education and Research (USA)
Unity Biotechnology, Inc. (USA)
Buck Institute for Research on Aging (USA)
Inventor
Laberge, Remi-Martin
Campisi, Judith
Davalos, Albert
Demaria, Marco
David, Nathaniel
Van Deursen, Jan M. A.
Baker, Darren J.
Childs, Bennett G.
Abstract
Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
A61K 31/428 - Thiazoles condensed with carbocyclic rings
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 47/36 - Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61P 11/00 - Drugs for disorders of the respiratory 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
Mayo Foundation for Medical Education and Research (USA)
Buck Institute for Research on Aging (USA)
Unity Biotechnology, Inc. (USA)
Inventor
Laberge, Remi-Martin
Campisi, Judith
Demaria, Marco
David, Nathaniel
Kirkland, James L.
Tchkonia, Tamar
Zhu, Yi
Abstract
Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
A61K 31/428 - Thiazoles condensed with carbocyclic rings
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 47/36 - Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 11/00 - Drugs for disorders of the respiratory 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
C07C 69/675 - Esters of carboxylic acids having esterified carboxyl groups bound to acyclic carbon atoms and having any of the groups OH, O-metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids of saturated hydroxy-carboxylic acids
Mayo Foundation for Medical Education and Research (USA)
Unity Biotechnology, Inc. (USA)
Inventor
Laberge, Remi-Martin
Campisi, Judith
Demaria, Marco
David, Nathaniel
Baker, Darren J.
Van Deursen, Jan M.A.
Davalos, Albert
Abstract
Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
A61P 11/00 - Drugs for disorders of the respiratory system
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61K 31/428 - Thiazoles condensed with carbocyclic rings
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
Disclosed herein are methods and compositions comprising alpha ketoglutarate (AKG) for altering senescence-associated secretory phenotype (SASP), and related diseases.
Disclosed herein are methods and compositions comprising alpha ketoglutarate (AKG) for altering senescence-associated secretory phenotype (SASP), and related diseases.
Various biological markers that function as indicators of the level of senescent cells in an organism are provided. In certain embodiments, the markers described herein (e.g., eicosanoids) can provide effective indicators of the presence and/or quantity of senescent cells in a subject (e.g., in a human or non-human mammal) and methods of identifying elevated levels of senescent cells in a mammal, and methods for determining the efficacy of senolytic agents, are provided.
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (France)
ASSISTANCE PUBLIQUE HOPITAUX DE PARIS (France)
BUCK INSTITUTE FOR RESEARCH ON AGING (USA)
Inventor
Neri, Christian
Farina, Francesca
Voisin, Jessica
Ellerby, Lisa
Abstract
The present invention relates pl6INK4a inhibitor, a composition of a pharmaceutical composition, for use in preventing and/or treating Huntington's disease, wherein said inhibitor is a nucleic acid or a peptide, a small compound molecule or a marketed drug.
A61P 25/14 - Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61K 31/00 - Medicinal preparations containing organic active ingredients
A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
44.
25-HYDROXYCHOLESTEROL (25HC), CRYAB AGGREGATION INHIBITOR, IS A NOVEL SENOLYTIC
Methods and compositions are provided herein that pertain to the discovery that the crystallin alpha B (CRYAB) gene and gene product provides an effective target for senolytic agents. In certain embodiments, methods of selectively killing one or more senescent cells in a subject in need thereof are provided wherein the method involves administering to the subject an effective amount of an agent that inhibits expression and/or aggregation of a CRYAB protein.
A61K 31/352 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. cannabinols, methantheline
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
45.
P16INK4A INHIBITOR FOR PREVENTING OR TREATING HUNTINGTON'S DISEASE
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (France)
ASSISTANCE PUBLIQUE HOPITAUX DE PARIS (France)
BUCK INSTITUTE FOR RESEARCH ON AGING (USA)
Inventor
Neri, Christian
Farina, Francesca
Voisin, Jessica
Ellerby, Lisa
Dancourt, Julia
Abstract
The present invention relates pl6INK4a inhibitor, a composition of a pharmaceutical composition, for use in preventing and/or treating Huntington's disease, wherein said inhibitor is a nucleic acid or a peptide, a small compound molecule or a marketed drug.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
C08F 293/00 - Macromolecular compounds obtained by polymerisation on to a macromolecule having groups capable of inducing the formation of new polymer chains bound exclusively at one or both ends of the starting macromolecule
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
47.
Substituted [1,2,3]triazolo[4,5-d]pyrimidines that lower stress-induced p-tau
In certain embodiments compounds corresponding in structure to the formula:
are provided that are effective to lower p-tau and/or to prevent or reduce elevation of p-tau, particularly in response to stress (e.g., elevated cortisol levels). The compounds are useful in the treatment or prophylaxis of pathologies characterized by abnormal amyloid plaque and or tangle formation and/or deposition.
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 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61P 1/04 - Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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
In certain embodiments hydantoin compounds are provided herein that are effective to inhibit BACE activity against APP. Without being bound to a particular theory, it is believed the activity of the hydantoins identified herein appears to be associated with binding to BACE and/or to APP particularly when these moieties form a BACE/APP complex. Accordingly, it is believed the compounds described herein represent a new class of compounds designated herein as APP-Binding-BACE Inhibitors (ABBIs) and provide a new mechanism to modulate APP processing. The hydantoins described herein appear to show improved brain permeability and functional BACE inhibition.
C07D 403/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 401/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/4168 - 1,3-Diazoles having a nitrogen atom attached in position 2, e.g. clonidine
A61K 31/4166 - 1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
50.
S-enantiomers of beta-hydroxybutyrate and butanediol and methods for using same
In various embodiments a compound comprising the enantiomerically enriched S-isomer S-BHB-S-1,3-butanediol is provided along with methods of use thereof.
C07C 69/675 - Esters of carboxylic acids having esterified carboxyl groups bound to acyclic carbon atoms and having any of the groups OH, O-metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids of saturated hydroxy-carboxylic acids
A23L 29/00 - Foods or foodstuffs containing additives; Preparation or treatment thereof
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
PONCE DE LEON HEALTH DESIGNATED ACTIVITY COMPANY (Ireland)
BUCK INSTITUTE FOR RESEARCH ON AGING (USA)
Inventor
Pereira, David
Weldon, Thomas
Abstract
Described herein are methods and compositions comprising nicotinamide riboside and alpha-ketoglutarate for treating frailty, for maintaining health, and for re-growing hair.
Mayo Foundation for Medical Education and Research (USA)
Unity Biotechnology, Inc. (USA)
Inventor
Laberge, Remi-Martin
Campisi, Judith
Demaria, Marco
David, Nathaniel
Kirkland, James L.
Tchkonia, Tamar
Zhu, Yi
Baker, Darren J.
Van Deursen, Jan M. A.
Abstract
Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
A61P 11/00 - Drugs for disorders of the respiratory system
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61K 31/428 - Thiazoles condensed with carbocyclic rings
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
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 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
In various embodiments constructs are provided for the delivery of an effector molecule into a cell. In certain embodiments the construct comprises a cell penetrating peptide (CPP) attached to an effector that is to be delivered into a cell, where the cell penetrating peptide comprises a Zika cell penetrating peptide (Zika CPP), and the effector is selected from the group consisting of a protein, a nucleic acid, an organic compound, a nanoparticle, a viral particle, and the like.
A61K 47/42 - Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 47/65 - Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
C07K 14/18 - Togaviridae, e.g. flavivirus, pestivirus, yellow fever virus, hepatitis C virus, japanese encephalitis virus
C12N 15/66 - General methods for inserting a gene into a vector to form a recombinant vector using cleavage and ligation; Use of non-functional linkers or adaptors, e.g. linkers containing the sequence for a restriction endonuclease
A61K 9/00 - Medicinal preparations characterised by special physical form
In various embodiments methods of utilizing gene drive constructs in asexual organisms such as viruses are provided. In certain embodiments the methods involve transfecting or infecting a cell with a modified DNA virus containing a gene drive construct; and infecting the cell with the target virus where the genome of said target DNA virus is modified by insertion of the gene drive construct into the genome of the target DNA virus and a population of modified target viruses (containing the gene drive construct) is produced.
C12N 15/63 - Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
C12N 15/66 - General methods for inserting a gene into a vector to form a recombinant vector using cleavage and ligation; Use of non-functional linkers or adaptors, e.g. linkers containing the sequence for a restriction endonuclease
In certain embodiments APP-specific BACE inhibitors (ASBIs) are provided as well as uses thereof. In certain embodiments methods of preventing delaying the onset of a pre-Alzheimer's condition and/or cognitive dysfunction, and/or ameliorating one or more symptoms of a pre-Alzheimer's condition and/or cognitive dysfunction, or preventing or delaying the progression of a pre-Alzheimer's condition or cognitive dysfunction to Alzheimer's disease are provided where the method involves administering to a subject in need thereof an APP specific BACE inhibitor (ASBI) in an amount sufficient to prevent or delay the onset of a pre-Alzheimer's cognitive dysfunction, and/or to ameliorate one or more symptoms of a pre-Alzheimer's cognitive dysfunction, and/or to prevent or delay the progression of a pre-Alzheimer's cognitive dysfunction to Alzheimer's disease. In certain embodiments the ASBI is a flavonoid (e.g. galangin) or flavonoid progrug (e.g., galangin prodrug).
C07D 311/30 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
A61K 31/352 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. cannabinols, methantheline
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
C07D 311/24 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
A61K 31/366 - Lactones having six-membered rings, e.g. delta-lactones
This invention creates a new paradigm for the treatment of age related conditions. As a consequence of aging, mutations arise in the genome of mitochondria in the body, which lessens their function as power providers for the cells in which they reside. To overcome this deficit, this disclosure provides new ways of preparing rejuvenated mitochondria that are tailored for administration to a subject who has manifest signs of an age related condition. Autologous mitochondria can be obtained, replicated (for example, in a producer cell line), and sorted for enhanced mitochondrial function such as capacity to generate ATP. The mitochondria are then transplanted back into the subject, with a view to rejuvenating energy generation capacity and ameliorating the signs and symptoms of the age-related condition.
A61K 35/12 - Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
C12N 1/00 - Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
C12N 5/071 - Vertebrate cells or tissues, e.g. human cells or tissues
C12N 15/00 - Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
C12N 5/02 - Propagation of single cells or cells in suspension; Maintenance thereof; Culture media therefor
C12P 1/00 - Preparation of compounds or compositions, not provided for in groups , by using microorganisms or enzymes; General processes for the preparation of compounds or compositions by using microorganisms or enzymes
57.
SYNTHESIS OF 3-HYDROXYBUTYRYL 3-HYDROXYBUTYRATE AND RELATED COMPOUNDS
Various biological markers that function as indicators of the level of senescent cells in an organism are provided. In certain embodiments, the markers described herein (e.g., eicosanoids) can provide effective indicators of the presence and/or quantity of senescent cells in a subject (e.g., in a human or non-human mammal) and methods of identifying elevated levels of senescent cells in a mammal, and methods for determining the efficacy of senolytic agents, are provided.
e.ge.ge.g., in a human or non-human mammal) and methods of identifying elevated levels of senescent cells in a mammal, and methods for determining the efficacy of senolytic agents, are provided.
A61K 31/197 - Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid (GABA), beta-alanine, epsilon-aminocaproic acid, pantothenic acid
A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
60.
TREATMENT OF OPHTHALMIC CONDITIONS SUCH AS MACULAR DEGENERATION, GLAUCOMA, AND DIABETIC RETINOPATHY USING PHARMACEUTICAL AGENTS THAT ELIMINATE SENESCENT CELLS
This invention is based on the discovery that many eye conditions associated with aging are mediated at least in part by cells bearing a senescent phenotype. Senescent cells accumulate with age, and express factors that contribute to the pathophysiology of age related conditions. The data show that in age-matched patients, the severity of age-related conditions correlates with the abundance of senescent cells, and that clearing senescent cells can help abrogate the condition. Small molecule drugs that remove senescent cells from affected tissue in the eye are provided as part of this invention that have special efficacy in treating ophthalmic conditions. They not only inhibit progression of the disease, they can also reverse some of the pathophysiology - such as neovascularization and vaso obliteration - that lead to vision loss. These senolytic agents have an appropriate dose and specificity profile to be effective in the clinical management of previously intractable ophthalmic conditions.
TREATMENT OF OPHTHALMIC CONDITIONS SUCH AS MACULAR DEGENERATION, GLAUCOMA, AND DIABETIC RETINOPATHY USING PHARMACEUTICAL AGENTS THAT ELIMINATE SENESCENT CELLS
This invention is based on the discovery that many eye conditions associated with aging are mediated at least in part by cells bearing a senescent phenotype. Senescent cells accumulate with age, and express factors that contribute to the pathophysiology of age related conditions. The data show that in age-matched patients, the severity of age-related conditions correlates with the abundance of senescent cells, and that clearing senescent cells can help abrogate the condition. Small molecule drugs that remove senescent cells from affected tissue in the eye are provided as part of this invention that have special efficacy in treating ophthalmic conditions. They not only inhibit progression of the disease, they can also reverse some of the pathophysiology - such as neovascularization and vaso obliteration - that lead to vision loss. These senolytic agents have an appropriate dose and specificity profile to be effective in the clinical management of previously intractable ophthalmic conditions.
This invention is based on the discovery that many lung diseases associated with aging are mediated at least in part by cells bearing a senescent phenotype. Senescent cells accumulate with age, and express factors that contribute to the pathophysiology of age related conditions. The severity of age-related conditions typically correlates with the abundance of senescent cells: thus, clearing senescent cells can help abrogate the condition: providing symptomatic relief, and potentially inhibiting disease progression. In accordance with this invention, a family of Bcl protein inhibitors has been developed for the treatment of lung diseases. These senolytic agents have an appropriate dose and specificity profile to be effective in the clinical management of previously intractable pulmonary diseases.
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61P 11/00 - Drugs for disorders of the respiratory system
63.
S-ENANTIOMERS OF BETA-HYDROXYBUTYRATE AND BUTANEDIOL AND METHODS FOR USING SAME
In various embodiments a compound comprising the enantiomerically enriched S-isomer S-BHB-S-1,3-butanediol is provided along with methods of use thereof.
C07C 69/675 - Esters of carboxylic acids having esterified carboxyl groups bound to acyclic carbon atoms and having any of the groups OH, O-metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids of saturated hydroxy-carboxylic acids
A61K 31/22 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
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
64.
Use of sulfonamide inhibitors of BCL-2 and BCL-xL to treat ophthalmic disease by selectively removing senescent cells
Mayo Foundation for Medical Education and Research (USA)
Inventor
Laberge, Remi-Martin
Campisi, Judith
Demaria, Marco
David, Nathaniel
Vasserot, Alain Philippe
Kirkland, James L.
Tchkonia, Tamar
Zhu, Yi
Baker, Darren J.
Childs, Bennett G.
Van Deursen, Jan M. A.
Abstract
Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
A61P 11/00 - Drugs for disorders of the respiratory system
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61K 31/428 - Thiazoles condensed with carbocyclic rings
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
In various embodiments a compound comprising the enantiomerically enriched S-isomer S-BHB-S-1,3-butanediol is provided along with methods of use thereof.
A61K 31/22 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
C07C 69/675 - Esters of carboxylic acids having esterified carboxyl groups bound to acyclic carbon atoms and having any of the groups OH, O-metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids of saturated hydroxy-carboxylic acids
The present invention provides a method of detecting senescent cells or diagnosing cellular senescence in a subject wherein the level of one or more selected mi RNAs is quantified in a sample from said subject.
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
67.
Substituted [1,2,3]triazolo[4,5-d]pyrimidines that lower stress-induced p-tau
Various [1,2,3]triazolo[4,5-d]pyrimidines are provided that are effective to lower p-tau and/or to prevent or reduce elevation of p-tau, particularly in response to stress (e.g., elevated cortisol levels). The compounds are useful in the treatment or prophylaxis of pathologies characterized by abnormal amyloid plaque and or tangle formation and/or deposition.
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
68.
FORMULATIONS FOR EXTENDING LIFESPAN AND HEALTHSPAN
Described herein are compositions for delaying onset or delaying progression of frailty, reversing aging phenotype, extending healthspan, compressing morbidity, increasing lifespan and reducing formation of senescent cells.
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
69.
FORMULATIONS FOR EXTENDING LIFESPAN AND HEALTHSPAN
Described herein are compositions for delaying onset or delaying progression of frailty, reversing aging phenotype, extending healthspan, compressing morbidity, increasing lifespan and reducing formation of senescent cells.
A61K 31/4745 - Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
Mayo Foundation for Medical Education and Research (USA)
Inventor
Laberge, Remi-Martin
Campisi, Judith
Demaria, Marco
David, Nathaniel
Baker, Darren J.
Kirkland, James L.
Tchkonia, Tamar
Zhu, Yi
Van Deursen, Jan M. A.
Vasserot, Alain Philippe
Childs, Bennett G.
Abstract
Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
A61K 9/00 - Medicinal preparations characterised by special physical form
A61P 11/00 - Drugs for disorders of the respiratory system
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61K 31/428 - Thiazoles condensed with carbocyclic rings
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
Mayo Foundation for Medical Education and Research (USA)
Inventor
Laberge, Remi-Martin
David, Nathaniel
Vasserot, Alain Philippe
Baker, Darren J.
Childs, Bennett G.
Kirkland, James L.
Tchkonia, Tamar
Van Deursen, Jan M. A.
Zhu, Yi
Abstract
Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
A61P 11/00 - Drugs for disorders of the respiratory system
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
A61K 31/428 - Thiazoles condensed with carbocyclic rings
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
Mayo Foundation for Medical Education and Research (USA)
Inventor
Laberge, Remi-Martin
Kirkland, James L.
Tchkonia, Tamar
Zhu, Yi
David, Nathaniel
Vasserot, Alain Philippe
Baker, Darren J.
Childs, Bennett G.
Van Deursen, Jan M. A.
Abstract
Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
A61P 11/00 - Drugs for disorders of the respiratory system
A61K 31/428 - Thiazoles condensed with carbocyclic rings
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
Mayo Foundation for Medical Education and Research (USA)
Inventor
Laberge, Remi-Martin
Campisi, Judith
Demaria, Marco
David, Nathaniel
Vasserot, Alain Philippe
Kirkland, James L.
Tchkonia, Tamar
Zhu, Yi
Baker, Darren J.
Childs, Bennett G.
Van Deursen, Jan M. A.
Abstract
Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
A61K 9/00 - Medicinal preparations characterised by special physical form
A61P 11/00 - Drugs for disorders of the respiratory system
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61K 31/428 - Thiazoles condensed with carbocyclic rings
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
In certain embodiments hydantoin compounds are provided herein that are effective to inhibit BACE activity against APP. Without being bound to a particular theory, it is believed the activity of the hydantoins identified herein appears to be associated with binding to BACE and/or to APP particularly when these moieties form a BACE/APP complex. Accordingly, it is believed the compounds described herein represent a new class of compounds designated herein as APP-Binding-BACE Inhibitors (ABBIs) and provide a new mechanism to modulate APP processing. The hydantoins described herein appear to show improved brain permeability and functional BACE inhibition.
A61K 31/4166 - 1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 401/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 403/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing aromatic rings
75.
Treatment of ophthalmic conditions by selectively removing senescent cells from the eye
Mayo Foundation for Medical Education and Research (USA)
Inventor
Laberge, Remi-Martin
Campisi, Judith
Demaria, Marco
David, Nathaniel
Vasserot, Alain Philippe
Kirkland, James L.
Tchkonia, Tamar
Zhu, Yi
Baker, Darren J.
Childs, Bennett G.
Van Deursen, Jan M. A.
Abstract
Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
Mayo Foundation for Medical Education and Research (USA)
Unity Biotechnology, Inc. (USA)
Buck Institute for Research on Aging (USA)
Inventor
Baker, Darren J.
Demaria, Marco
Davalos, Albert
Childs, Bennett G.
Van Deursen, Jan M. A.
Kirkland, James L.
Tchkonia, Tamar
Zhu, Yi
David, Nathaniel
Laberge, Remi-Martin
Campisi, Judith
Abstract
Foamy macrophages with senescence markers accumulate in the subendothelial space at the onset of atherosclerosis where they drive pathology by increasing expression of key atherogenic and inflammatory cytokines and chemokines. In advanced lesions, senescent cells promote features of plaque instability, including elastic fiber degradation and fibrous cap thinning, by heightening metalloprotease production. This invention provides methods and materials for treating arthritis by removing senescent cells in or around atherosclerotic plaques, thereby stabilizing the plaques, inhibiting rupture of the plaques and pathological sequelae that manifest as coronary artery disease.
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
A61K 31/428 - Thiazoles condensed with carbocyclic rings
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 9/00 - Medicinal preparations characterised by special physical form
In various embodiments a cancer treatment method is provided based on inhibition of proline catabolism. When combined with p53 restoration therapy and/or inhibition of glutaminase, the inhibition of proline catabolism results in a “synthetic lethal” and synergistic anticancer response. Novel suicide inhibitors that induce the degradation of proline dehydrogenase (PRODH) are also provided. Also provided is a method of assaying PRODH to identify responders/non-responders to inhibition of proline catabolism and/or glutaminase.
A61K 31/198 - Alpha-amino acids, e.g. alanine, edetic acid (EDTA)
C07C 229/30 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and unsaturated
C07C 229/20 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups
C07C 229/06 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer
A61K 31/341 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
A61K 31/501 - Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
78.
Use of sulfonamide inhibitors of Bcl-2 to treat senescence-associated lung conditions such as pulmonary fibrosis and chronic obstructive pulmonary disease
MAYO FOUNDATION FOR MEDICAL EDUCATIOIN AND RESEARCH (USA)
Inventor
Laberge, Remi-Martin
Campisi, Judith
Demaria, Marco
David, Nathaniel
Baker, Darren J.
Kirkland, James L.
Tchkonia, Tamar
Van Deursen, Jan M. A.
Zhu, Yi
Abstract
Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
A61K 31/537 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one oxygen as the ring hetero atoms, e.g. 1,2-oxazines spiro-condensed or forming part of bridged ring systems
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
A61K 31/428 - Thiazoles condensed with carbocyclic rings
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 9/00 - Medicinal preparations characterised by special physical form
In various embodiments, compositions and methods are provided for treatment and/or prevention of amyloidogenic diseases. In certain embodiments, the methods entail administering an effective amount of compound C41 to a subject in need thereof for prophylactic or therapeutic effect. The methods are particularly useful for prophylactic and therapeutic treatment of Alzheimer's disease. In certain embodiments, methods of reducing the risk, lessening the severity, or delaying the progression or onset of a disease characterized by beta-amyloid deposits in the brain of a mammal are also provided. In certain embodiments, methods of directly or indirectly enhances sAPPa, lowers Aß, p-Tau, inhibits the C-terminal cleavage of APP resulting in the formation of APP-C31 peptide and APPneo (APP664) and improves memory in a mammal are provided.
MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH (USA)
Inventor
David, Nathaniel
Davalos, Albert
Laberge, Remi-Martin
Campisi, Judith
Demaria, Marco
Vasserot, Alain
Kim, Chaekyu
Jeon, Okhee
Elisseeff, Jennifer
Kirkland, James L.
Tchkonia, Tamar
Zhu, Yi
Abstract
This disclosure provides a technology for managing the sensation of pain in a subject in need thereof. Treatment methods according to this invention include administering to the subject a formulation that contains an effective amount of (4-[(4S,5R)-4,5-bis(4-chlorophenyl)-4,5-dihydro-2-[4-methoxy-2-(1-methylethoxy)phenyl]-1H-imidazol-1-yl]carbonyl]-2-piperazinone).
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
A61K 31/428 - Thiazoles condensed with carbocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
In various embodiments, compositions and methods are provided for treatment and/or prevention of amyloidogenic diseases. In certain embodiments, the methods entail administering an effective amount of compound C41 to a subject in need thereof for prophylactic or therapeutic effect. The methods are particularly useful for prophylactic and therapeutic treatment of Alzheimer's disease. In certain embodiments, methods of reducing the risk, lessening the severity, or delaying the progression or onset of a disease characterized by beta-amyloid deposits in the brain of a mammal are also provided. In certain embodiments, methods of directly or indirectly enhances sAPPα, lowers Aβ, p-Tau, inhibits the C-terminal cleavage of APP resulting in the formation of APP-C31 peptide and APPneo (APP664) and improves memory in a mammal are provided.
MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH (USA)
Inventor
Laberge, Remi-Martin
Campisi, Judith
Davalos, Albert
Demaria, Marco
David, Nathaniel
Vasserot, Alain Philippe
Kirkland, James L.
Tchkonia, Tamar
Van Deursen, Jan M. A.
Elisseeff, Jennifer
Kim, Chaekyu
Jeon, Okhee
Zhu, Yi
Abstract
Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/428 - Thiazoles condensed with carbocyclic rings
Mayo Foundation for Medical Education and Research (USA)
The John Hopkins University (USA)
Inventor
Laberge, Remi-Martin
Campisi, Judith
Davalos, Albert
Demaria, Marco
David, Nathaniel
Vasserot, Alain Philippe
Kirkland, James L.
Tchkonia, Tamar
Elisseeff, Jennifer
Kim, Chaekyu
Jeon, Okhee
Zhu, Yi
Abstract
Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH (USA)
Inventor
Laberge, Remi-Martin
Campisi, Judith
Davalos, Albert
Demaria, Marco
David, Nathaniel
Zhu, Yi
Kirkland, James L.
Tchkonia, Tamar
Abstract
Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
G01N 1/00 - Sampling; Preparing specimens for investigation
C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
A61K 31/428 - Thiazoles condensed with carbocyclic rings
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
Mayo Foundation for Medical Education and Research (USA)
The John Hopkins University (USA)
Inventor
Laberge, Remi-Martin
Campisi, Judith
Davalos, Albert
Demaria, Marco
David, Nathaniel
Vasserot, Alain Philippe
Kirkland, James L.
Tchkonia, Tamar
Zhu, Yi
Elisseeff, Jennifer
Kim, Chaekyu
Jeon, Okhee
Abstract
Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
Methods are provided herein for enhancing the effectiveness of medical therapies by administering agents that suppress a biological damage response that is inducible by the medical therapy administered to a subject. In certain embodiments, a method is provided for administering an anti-senescent cell agent that suppresses a biological response comprising cellular senescence that is induced by the medical therapy.
A61P 35/04 - Antineoplastic agents specific for metastasis
A61K 31/56 - Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
A61K 31/352 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. cannabinols, methantheline
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
87.
Lipoic acid and derivatives thereof for the treatment of cystinuria
In various embodiments methods and composition are provided for the treatment and/or prophylaxis of cystinuria. In certain embodiments the methods involve administering to a mammal in need thereof (e.g., identified as at risk for, or having cystinuria) an effective amount of lipoic acid and/or one or more lipoic acid derivatives.
The invention described herein relates to novel personalized methods for treating, reducing or reversing cognitive decline utilizing a number of cognitive biological functions (factors), including metabolic parameters.
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
A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
A61K 31/436 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
90.
Transgenic mouse for determining the role of senescent cells in cancer
Erasmus University Medical Center Rotterdam (Netherlands)
Inventor
Campisi, Judith
Demaria, Marco
Rodier, Francis
Laberge, Remi-Martin
Mitchell, James
Hoeijmakers, Jan H. J.
Toussaint, Wendy
Abstract
INK4a promoter sequence that controls expression of a protein such that it is expressed preferentially in senescent cells. The protein either directly induces apoptosis, or converts a prodrug to a cytotoxic compound. In addition, the mouse is injected with syngeneic tumor cells, or has second transgene that causes tumors to form. Removing senescent cells from the mouse may result in the formation of fewer tumors.
Erasmus University Medical Center Rotterdam (Netherlands)
Inventor
Campisi, Judith
Demaria, Marco
Laberge, Remi-Martin
Rodier, Francis
Mitchell, James
Hoeijmakers, Jan H. J.
Toussaint, Wendy
Abstract
This invention provides a transgenic mouse for studying the role of senescent cells on an age-related disorder or an age-sensitive trait. The transgene contains a p16 promoter sequence that controls expression of an enzyme so as to cause the enzyme to be expressed in senescent cells in the mouse. The enzyme converts a prodrug to a cytotoxic agent, so that treating the mouse with the prodrug results in the prodrug selectively killing the senescent cells. As a result, progression of an age-related disorder or an age-sensitive trait is delayed. Included is the 3MR mouse model, which also expresses bioluminescent and fluorescent markers under control of the p16 promoter so that senescent cells in the mice can be visualized.
MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH (USA)
Inventor
Laberge, Remi-Martin
Campisi, Judith
Davalos, Albert
Demaria, Marco
David, Nathaniel
Vasserot, Alain Philippe
Baker, Darren J.
Childs, Bennett G.
Kirkland, James L.
Tchkonia, Tamar
Van Deursen, Jan M.A.
Zhu, Yi
López-Domínguez, José Alberto
Abstract
Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders. Also included herein are methods for extending lifespan.
A61K 38/48 - Hydrolases (3) acting on peptide bonds (3.4)
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
In certain embodiments compounds of the formula: (e.g., triazolopyrimidine(s) and/or triazolopyridine(s)) are provided that are effective to lower p- tau and/or to prevent or reduce elevation of p-tau, particularly in response to stress (e.g., elevated cortisol levels). The compounds are useful in the treatment or prophylaxis of pathologies characterized by abnormal amyloid plaque and or tangle formation and/or deposition.
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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
94.
TRIAZOLOPYRIDINES AND TRIAZOLOPYRIMIDINES THAT LOWER STRESS-INDUCED P-TAU
In certain embodiments compounds (e.g., triazolopyrimidine(s) and/or triazolopyridine(s)) are provided that are effective to lower p-tau and/or to prevent or reduce elevation of p-tau, particularly in response to stress (e.g., elevated cortisol levels). The 5 compounds are useful in the treatment or prophylaxis of pathologies characterized by abnormal amyloid plaque and or tangle formation and/or deposition.
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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
95.
COMPOUNDS AND USES IN TREATMENT OF SENESCENCE-ASSOCIATED CONDITONS
Disclosed herein are compounds that are effective for treatment of various disease states. Dosing includes both single administration and regimens of cycling dosages.
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61P 43/00 - Drugs for specific purposes, not provided for in groups
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
In certain embodiments hydantoin compounds are provided herein that are effective to inhibit BACE activity against APP. Without being bound to a particular theory, it is believed the activity of the hydantoins identified herein appears to be associated with binding to BACE and/or to APP particularly when these moieties form a BACE/APP complex. Accordingly, it is believed the compounds described herein represent a new class of compounds designated herein as APP-Binding-BACE Inhibitors (ABBIs) and provide a new mechanism to modulate APP processing. The hydantoins described herein appear to show improved brain permeability and functional BACE inhibition.
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/4168 - 1,3-Diazoles having a nitrogen atom attached in position 2, e.g. clonidine
A61K 31/4166 - 1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
C07D 401/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
C07D 403/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing aromatic rings
97.
INHIBITION OF PROLINE CATABOLISM FOR THE TREATMENT OF CANCER AND OTHER THERAPEUTIC APPLICATIONS
In various embodiments a cancer treatment method is provided based on inhibition of proline catabolism. When combined with p53 restoration therapy and/or inhibition of glutaminase, the inhibition of proline catabolism results in a "synthetic lethal" and synergistic anticancer response. Novel suicide inhibitors that induce the degradation of proline dehydrogenase (PRODH) are also provided. Also provided is a method of assaying PRODH to identify responders/non-responders to inhibition of proline catabolism and/or glutaminase.
A61K 31/498 - Pyrazines or piperazines ortho- or peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61K 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A link between ApoE4 allele and sirtuins expression level is identified that is believed to be associated with elevated risk for the promotion of processing of amyloid precursor protein (APP) by the non-amyloidogenic pathway in a mammal leading to elevated risk for Alzheimer's disease. Compounds are identified that upregulate sirtuins (e.g., SirT1) expression levels and appear to be useful in the treatment and/or prophylaxis of MCI and/or Alzheimer's disease.
C07C 219/10 - Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having at least one of the hydroxy groups esterified by a carboxylic acid having the esterifying carboxyl group bound to an acyclic carbon atom of a carbon skeleton containing rings
C07C 219/14 - Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having at least one of the hydroxy groups esterified by a carboxylic acid having the esterifying carboxyl group bound to a carbon atom of a six-membered aromatic ring
A61K 31/165 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
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
99.
Hydantoins that modulate bace-mediated app processing
In certain embodiments hydantoin compounds are provided herein that are effective to inhibit BACE activity against APP. Without being bound to a particular theory, it is believed the activity of the hydantoins identified herein appears to be associated with binding to BACE and/or to APP particularly when these moieties form a BACE/APP complex. Accordingly, it is believed the compounds described herein represent a new class of compounds designated herein as APP-Binding-BACE Inhibitors (ABBIs) and provide a new mechanism to modulate APP processing. The hydantoins described herein appear to show improved brain permeability and functional BACE inhibition.
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 401/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 403/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing aromatic rings
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/4166 - 1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
A61K 31/4168 - 1,3-Diazoles having a nitrogen atom attached in position 2, e.g. clonidine
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
100.
APP specific BACE inhibitors (ASBIs) and uses thereof
In certain embodiments APP-specific BACE inhibitors (ASBIs) are provided as well as uses thereof. In certain embodiments methods of preventing or delaying the onset of a pre-Alzheimer's condition and/or cognitive dysfunction, and/or ameliorating one or more symptoms of a pre-Alzheimer's condition and/or cognitive dysfunction, or preventing or delaying the progression of a pre-Alzheimer's condition or cognitive dysfunction to Alzheimer's disease are provided where the method involves administering to a subject in need thereof an APP specific BACE inhibitor (ASBI) in an amount sufficient to prevent or delay the onset of a pre-Alzheimer's cognitive dysfunction, and/or to ameliorate one or more symptoms of a pre-Alzheimer's cognitive dysfunction, and/or to prevent or delay the progression of a pre-Alzheimer's cognitive dysfunction to Alzheimer's disease. In certain embodiments the ASBI is a flavonoid (e.g. galangin) or flavonoid prodrug (e.g., galangin prodrug).
A61K 31/352 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. cannabinols, methantheline
A61K 31/366 - Lactones having six-membered rings, e.g. delta-lactones
C07D 311/24 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
patents
