A method to evaluate individuals with certain neurodegenerative diseases (e.g., Parkinson's Disease) in relation to etiologic diagnosis, prognosis and response to therapy involving the noninvasive collection of a biologic sample (e.g., venous blood), isolation of small, neuronally-derived, extracellular vesicles (e.g., exosomes), assay of their external and/or internal contents for quantities of informative biomarkers (e.g., signaling kinases, catalytic proteins and miRNA species) for the construction of a diagnostic/prognostic/response algorithms of clinical utility.
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
C12Q 1/48 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving transferase
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
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
G16H 20/10 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for calculating health indicesICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
G16H 50/70 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for mining of medical data, e.g. analysing previous cases of other patients
The present invention describes the combination of a 5HT3-antagonist and/or NK1-antagonist with pramipexole to reduce or eliminate the adverse effects associated with the use of pramipexole and to enable the use of high doses of pramipexole for treating anhedonia.
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 31/439 - 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 the ring forming part of a bridged ring system, e.g. quinuclidine
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
3.
KINASES AS BIOMARKERS FOR NEURODEGENERATIVE CONDITIONS
An assay for using signaling kinases alone or in combination with oligomeric forms of neurodegenerative proteins can include: a) providing a biological sample, e.g., a blood sample, from a subject; b) enriching for neuronally (e.g., central nervous system (“CNS”)) derived microparticles, e.g., exosomes, from the blood sample; c) removing proteins from the surface of the isolated exosomes to produce scrubbed exosomes; d) determining, in the isolated internal contents, set of biomarkers including: (1) at least one signaling kinase and, optionally, at least one oligomeric form of a neurodegenerative protein; or (2) a plurality of different signaling kinases.
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 31/366 - Lactones having six-membered rings, e.g. delta-lactones
G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
G16H 50/70 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for mining of medical data, e.g. analysing previous cases of other patients
G16H 70/60 - ICT specially adapted for the handling or processing of medical references relating to pathologies
4.
DIAGNOSTIC INDICES FOR NEURODEGENERATIVE CONDITIONS
A method to evaluate individuals with certain neurodegenerative diseases (e.g., Parkinson's Disease) in relation to etiologic diagnosis, prognosis and response to therapy involving the noninvasive collection of a biologic sample (e.g., venous blood), isolation of small, neuronally-derived, extracellular vesicles (e.g., exosomes), assay of their external and/or internal contents for quantities of informative biomarkers (e.g., signaling kinases, catalytic proteins and miRNA species) for the construction of a diagnostic/prognostic/response algorithms of clinical utility.
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
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
An assay for alpha synuclein and its various forms includes: a) providing a blood sample from a subject; b) isolating central nervous system (“CNS”) derived exosomes from the blood sample; c) removing proteins from the surface of the isolated exosomes to produce scrubbed exosomes; d) isolating the internal contents of the scrubbed exosomes; e) determining, in the isolated internal contents, a quantitative measure of oligomeric α-synuclein protein and, optionally, one or a plurality of protein forms selected from: monomeric α-synuclein, phosphorylated α-synuclein, monomeric tau, oligomeric tau, phosphorylated tau, amyloid beta (“a-beta”) 1-40, amyloid beta 1-42, and oligomeric amyloid beta; f) separating species of oligomeric α-synuclein into a plurality of fractions; g) determining a quantitative measure of each of one or a plurality of the separated oligomeric α-synuclein species and, optionally, one or a plurality of species selected from: monomeric α-synuclein, tau-synuclein co-polymers, amyloid beta-synuclein co-polymers and tau-amyloid beta-synuclein co-polymers.
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
G16H 10/20 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for electronic clinical trials or questionnaires
6.
DOMPERIDONE COMPOSITIONS AND METHODS FOR TREATING DEPRESSION
The present invention describes the combination of domperidone with pramipexole or a pharmaceutically acceptable salt or solvate thereof, useful for treating depressive disorders, including major depressive disorder.
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A pharmaceutical combination comprising domperidone, a 6-propylamino-4,5,6,7-tetrahydro-1,3-benzothiazole-2-amine and at least one of fluoxetine, zonisamide or a statin, for the treatment of protein misfolding neurodegenerative diseases.
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
An assay for using signaling kinases alone or in combination with oligomeric forms of neurodegenerative proteins can include: a) providing a biological sample, e.g., a blood sample, from a subject; b) enriching for neuronally (e.g., central nervous system ("CNS")) derived microparticles, e.g., exosomes, from the blood sample; c) removing proteins from the surface of the isolated exosomes to produce scrubbed exosomes; d) determining, in the isolated internal contents, set of biomarkers including: (1) at least one signaling kinase and, optionally, at least one oligomeric form of a neurodegenerative protein; or (2) a plurality of different signaling kinases.
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
Provided herein are methods of developing pharmaceuticals for treatment of neurodegenerative conditions, such as synucleopathic conditions, amyloidopathic conditions, tauopathic conditions, and Huntington's disease. The methods involve using a biomarker to determine the effect of a candidate pharmaceutical on the condition. The biomarker profile includes quantitative measures of each of one or a plurality of neurodegenerative protein forms, wherein the neurodegenerative proteins are, e.g., alpha-synuclein and, amyloid beta, tau or huntingtin. Biomarker profiles include one or more oligomeric forms and, optionally, one or more monomeric forms of the neurodegenerative protein. Neurodegenerative proteins can be quantified from, e.g., CNS-derived exosomes from the blood of a subject.
The present invention describes the combination of a 6-propylamino-4,5,6,7-tetrahydro-1,3-benzothiazole-2-amine or of a pharmaceutically acceptable salt or solvate thereof with fluoxetine or a pharmaceutically acceptable salt or solvate thereof, for use for treating a synucleinopathy such as Parkinson's disease, Lewy body disease, mutations in the glucocerebrosidase gene, or multiple system atrophy.
An assay for alpha synuclein and its various forms includes: a) providing a blood sample from a subject; b) isolating central nervous system ("CNS") derived exosomes from the blood sample; c) removing proteins from the surface of the isolated exosomes to produce scrubbed exosomes; d) isolating the internal contents of the scrubbed exosomes; e) determining, in the isolated internal contents, a quantitative measure of oligomeric α-synuclein protein and, optionally, one or a plurality of protein forms selected from: monomeric α-synuclein, phosphorylated α-synuclein, monomeric tau, oligomeric tau, phosphorylated tau, amyloid beta ("a-beta") 1-40, amyloid beta 1-42, and oligomeric amyloid beta; f) separating species of oligomeric α-synuclein into a plurality of fractions; g) determining a quantitative measure of each of one or a plurality of the separated oligomeric α-synuclein species and, optionally, one or a plurality of species selected from: monomeric α-synuclein, tau-synuclein co-polymers, amyloid beta-synuclein co-polymers and tau-amyloid beta-synuclein co-polymers.
C12N 1/02 - Separating microorganisms from their culture media
C12N 5/071 - Vertebrate cells or tissues, e.g. human cells or tissues
G01N 27/62 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating the ionisation of gases, e.g. aerosolsInvestigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electric discharges, e.g. emission of cathode
A pharmaceutical combination comprising domperidone, a 6-propylamino-4,5,6,7-tetrahydro-1,3-benzothiazole-2-amine and at least one of fluoxetine, zonisamide or a statin, for the treatment of protein misfolding neurodegenerative diseases.
A61K 31/438 - 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 the ring being spiro-condensed with carbocyclic or heterocyclic ring systems
A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
The present invention describes the combination of domperidone with pramipexole or a pharmaceutically acceptable salt or solvate thereof, useful for treating depressive disorders, including major depressive disorder.
The present invention provides a pharmaceutical combination comprising an inhibitor of dopamine agonist adverse effects and a dopamine agonist, for treating Parkinson's disease and Parkinson's disease-related disorders.
A61K 31/198 - Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
A61K 31/5415 - 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 sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
A61K 9/00 - Medicinal preparations characterised by special physical form
15.
ANTI-NEURODEGENERATIVE COMBINATIONS AND USE FOR TREATMENT OF NEURODEGENERATIVE DISEASES
The present invention provides a combination of a 5HT3-antagonist and/or a NK-1 antagonist with 6-propylamino-4,5,6,7-tetrahydro-1,3-benzothiazole-2-amine and with fluoxetine or a pharmaceutically acceptable salt or solvate thereof, zonisamide or a pharmaceutically acceptable salt or solvate thereof, or a statin or a pharmaceutically acceptable salt or solvate thereof, for use for treating a protein misfolding neurodegenerative disease such as Alzheimer's disease, Lewy body disease, Parkinson's disease, or Huntington's disease.
A61K 31/403 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
The present invention describes the use of a 5HT3-antagonist, in combination with a 6-propylamino-4,5,6,7-tetrahydro-1,3-benzothiazole-2-amine, to reduce adverse effects and to facilitate the neuroprotective treatment of a patient suffering from a synucleinopathic disorder to enable a therapeutically effective 6-propylamino-4,5,6,7-tetrahydro-1,3-benzothiazole-2-amine daily dose without the dose-limiting adverse effects caused by pramipexole when administered alone.
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
A61K 31/439 - 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 the ring forming part of a bridged ring system, e.g. quinuclidine
17.
METHODS FOR DEVELOPING PHARMACEUTICALS FOR TREATING NEURODEGENERATIVE CONDITIONS
Provided herein are methods of developing pharmaceuticals for treatment of neurodegenerative conditions, such as synucleopathic conditions, amyloidopathic conditions, tauopathic conditions, and Huntington's disease. The methods involve using a biomarker to determine the effect of a candidate pharmaceutical on the condition. The biomarker profile includes quantitative measures of each of one or a plurality of neurodegenerative protein forms, wherein the neurodegenerative proteins are, e.g., alpha-synuclein and, amyloid beta, tau or huntingtin. Biomarker profiles include one or more oligomeric forms and, optionally, one or more monomeric forms of the neurodegenerative protein. Neurodegenerative proteins can be quantified from, e.g., CNS-derived exosomes from the blood of a subject.
The present invention describes pharmaceutical combinations, compositions, and methods comprising a statin and 6-propylamino-4,5,6,7-tetrahydro-1,3- benzothiazole-2-amine or a pharmaceutically acceptable salt and/or solvate thereof, 5 that are useful for the treatment of synucleinopathic disorders.
A61K 31/22 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
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
19.
NK-1 ANTAGONIST COMPOSITIONS AND METHODS FOR USE IN TREATING DEPRESSION
The present invention describes the combination of a NK1-antagonist with pramipexole or a pharmaceutically acceptable salt or solvate thereof, useful for treating depressive disorders, including major depressive disorder.
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/396 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having three-membered rings, e.g. aziridine
The present invention relates to a combination of zonisamide with pramipexole or a pharmaceutically acceptable salt or solvate of pramipexole for treating a synucleinopathy.
The present invention describes the combination of a 5HT3-antagonist with pramipexole to reduce or eliminate the adverse effects associated with the use of pramipexole and to enable the use of high doses of pramipexole, useful for treating depressive disorders such as major depressive disorder.
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
A61K 31/439 - 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 the ring forming part of a bridged ring system, e.g. quinuclidine
A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
22.
NK1-ANTAGONIST COMBINATION AND METHOD FOR TREATING SYNUCLEINOPATHIES
The present invention describes the use of a NK1-antagonist, in combination with 6- propylamino-4,5,6,7-tetrahydro-1,3-benzothiazole-2-amine, to facilitate the treatment of a patient suffering from a synucleinopathy by enabling a therapeutically effective 6-propylamino-4,5,6,7-tetrahydro-1,3-benzothiazole-2-amine daily dose to act without the typical adverse effects caused by pramipexole dihydrochloride monohydrate when administered alone.
A61K 31/438 - 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 the ring being spiro-condensed with carbocyclic or heterocyclic ring systems
A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
C07D 401/00 - 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
C07D 401/02 - 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
C07D 403/04 - 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 directly linked by a ring-member-to-ring- member bond
23.
PHARMACEUTICAL COMBINATION AND ITS USE FOR TREATING SYNUCLEINOPATHIES
The present invention describes the combination of a 6-propylamino-4,5,6,7-tetrahydro-1,3-benzothiazole-2-amine or of a pharmaceutically acceptable salt or solvate thereof with fluoxetine or a pharmaceutically acceptable salt or solvate thereof, for use for treating a synucleinopathy such as Parkinson's disease, Lewy body disease, mutations in the glucocerebrosidase gene, or multiple system atrophy.
The present invention describes the use of a 5HT3-antagonist, in combination with a 6-propylamino-4,5,6,7-tetrahydro-1,3-benzothiazole-2-amine, to reduce adverse effects and to facilitate the neuroprotective treatment of a patient suffering from a synucleinopathic disorder to enable a therapeutically effective 6-propylamino-4,5,6,7-tetrahydro-1,3-benzothiazole-2-amine daily dose without the dose-limiting adverse effects caused by pramipexole when administered alone.
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
A61K 31/439 - 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 the ring forming part of a bridged ring system, e.g. quinuclidine
A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
25.
NK1-ANTAGONIST COMBINATION AND METHOD FOR TREATING SYNUCLEINOPATHIES
The present invention describes the use of a NK1-antagonist, in combination with 6- propylamino-4,5,6,7-tetrahydro-1,3-benzothiazole-2-amine, to facilitate the treatment of a patient suffering from a synucleinopathy by enabling a therapeutically effective 6-propylamino-4,5,6,7-tetrahydro-1,3-benzothiazole-2-amine daily dose to act without the typical adverse effects caused by pramipexole dihydrochloride monohydrate when administered alone.
A61K 31/438 - 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 the ring being spiro-condensed with carbocyclic or heterocyclic ring systems
A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
C07D 401/00 - 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
C07D 401/02 - 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
C07D 403/04 - 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 directly linked by a ring-member-to-ring- member bond
26.
COMPOSITION COMPRISING PRAMIPEXOLE AND 5HT3 ANTAGONIST FOR TREATING DEPRESSION
The present invention describes the combination of a 5HT3-antagonist with pramipexole to reduce or eliminate the adverse effects associated with the use of pramipexole and to enable the use of high doses of pramipexole, useful for treating depressive disorders such as major depressive disorder.
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
A61K 31/428 - Thiazoles condensed with carbocyclic rings
A61K 31/439 - 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 the ring forming part of a bridged ring system, e.g. quinuclidine
A61K 31/46 - 8-Azabicyclo [3.2.1] octaneDerivatives thereof, e.g. atropine, cocaine
A61K 31/538 - 1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with carbocyclic ring systems
The present invention describes the combination of a NK1-antagonist with pramipexole or a pharmaceutically acceptable salt or solvate thereof, useful for treating depressive disorders, including major depressive disorder.
A61K 31/428 - Thiazoles condensed with carbocyclic rings
A61K 31/438 - 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 the ring being spiro-condensed with carbocyclic or heterocyclic ring systems
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
An assay for using signaling kinases alone or in combination with oligomeric forms of neurodegenerative proteins can include: a) providing a biological sample, e.g., a blood sample, from a subject; b) enriching for neuronally (e.g., central nervous system ("CNS")) derived microparticles, e.g., exosomes, from the blood sample; c) removing proteins from the surface of the isolated exosomes to produce scrubbed exosomes; d) determining, in the isolated internal contents, set of biomarkers including: (1) at least one signaling kinase and, optionally, at least one oligomeric form of a neurodegenerative protein; or (2) a plurality of different signaling kinases.
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
The present invention describes the use of a 5HT3-antagonist, in combination with a 6-propylamino-4,5,6,7-tetrahydro-l,3-benzothiazole-2-amine, to reduce adverse effects and to facilitate the neuroprotective treatment of a patient suffering from a synucleinopathic disorder to enable a therapeutically effective 6-propylamino-4,5,6,7-tetrahydro-l,3-benzothiazole-2-amine daily dose without the dose-limiting adverse effects caused by pramipexole when administered alone.
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
A61K 31/439 - 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 the ring forming part of a bridged ring system, e.g. quinuclidine
A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
30.
METHODS FOR DEVELOPING PHARMACEUTICALS FOR TREATING NEURODEGENERATIVE CONDITIONS
Provided herein are methods of developing pharmaceuticals for treatment of neurodegenerative conditions, such as synucleopathic conditions, amyloidopathic conditions, tauopathic conditions, and Huntington's disease. The methods involve using a biomarker to determine the effect of a candidate pharmaceutical on the condition. The biomarker profile includes quantitative measures of each of one or a plurality of neurodegenerative protein forms, wherein the neurodegenerative proteins are, e.g., alpha-synuclein and, amyloid beta, tau or huntingtin. Biomarker profiles include one or more oligomeric forms and, optionally, one or more monomeric forms of the neurodegenerative protein. Neurodegenerative proteins can be quantified from, e.g., CNS-derived exosomes from the blood of a subject.
An assay for alpha synuclein and its various forms includes: a) providing a blood sample from a subject; b) isolating central nervous system ("CNS") derived exosomes from the blood sample; c) removing proteins from the surface of the isolated exosomes to produce scrubbed exosomes; d) isolating the internal contents of the scrubbed exosomes; e) determining, in the isolated internal contents, a quantitative measure of oligomeric a-synuclein protein and, optionally, one or a plurality of protein forms selected from: monomeric a-synuclein, phosphorylated a-synuclein, monomeric tau, oligomeric tau, phosphorylated tau, amyloid beta ("a-beta") 1-40, amyloid beta 1-42, and oligomeric amyloid beta; f) separating species of oligomeric a-synuclein into a plurality of fractions; g) determining a quantitative measure of each of one or a plurality of the separated oligomeric a-synuclein species and, optionally, one or a plurality of species selected from: monomeric a-synuclein, tau-synuclein co-polymers, amyloid beta-synuclein co-polymers and tau-amyloid beta-synuclein co-polymers.
C12N 1/02 - Separating microorganisms from their culture media
C12N 5/071 - Vertebrate cells or tissues, e.g. human cells or tissues
G01N 27/62 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating the ionisation of gases, e.g. aerosolsInvestigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electric discharges, e.g. emission of cathode
The present invention describes the combination of a 6-propylamino-4,5,6,7-tetrahydro-1,3-benzothiazole-2-amine or of a pharmaceutically acceptable salt or solvate thereof with fluoxetine or a pharmaceutically acceptable salt or solvate thereof, for use for treating a synucleinopathy such as Parkinson's disease, Lewy body disease, mutations in the glucocerebrosidase gene, or multiple system atrophy.
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
33.
DIAGNOSTIC INDICES FOR NEURODEGENERATIVE CONDITIONS
A method to evaluate individuals with certain neurodegenerative diseases (e.g., Parkinson's Disease) in relation to etiologic diagnosis, prognosis and response to therapy involving the noninvasive collection of a biologic sample (e.g., venous blood), isolation of small, neuronally-derived, extracellular vesicles (e.g., exosomes), assay of their external and/or internal contents for quantities of informative biomarkers (e.g., signaling kinases, catalytic proteins and miRNA species) for the construction of a diagnostic/prognostic/response algorithms of clinical utility.
C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions
G01N 33/48 - Biological material, e.g. blood, urineHaemocytometers
G16B 40/00 - ICT specially adapted for biostatisticsICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
patents
