158 results about "Huntingtons chorea" patented technology

Among other tilings, the present disclosure provides various technologies including chirally controlled oligonucleotide compositions and technologies for manufacturing and using such oligonucleotide compositions. In some embodiments, the present disclosure provides technologies useful for allele-specific knockdown of mutant Huntingtin transcripts. In some embodiments, the present disclosure provides technologies usefill for reducing the expression, level, amount, and / or activity of mutant Huntingtin transcripts or products thereof. In some embodiments, the present disclosure provides methods for treating Huntington's disease.

Alkoxy-substituted N-benzyl-2-phenylacetamide compounds and derivatives are G-protein coupled receptor (GPR) 88 modulators for use in the treatment of a disease mediated by GPR88. Indications include Tourette's Syndrome, Huntington's Disease (HD), Addiction, Parkinson's Disease (PD), Schizophrenia, and Attention Deficit Hyperactivity Disorder (ADHD), choreiform movements, speech delay, learning disabilities, depression, hyperkinetic movement disorders characterised by chorea and / or dystonia, psychosis, cognitive deficits in schizophrenia, affective disorders, bipolar disorder, Alzheimer's disease and basal ganglia disorders.

Aspects of the disclosure relate to compositions and methods useful for treating Huntington's disease. In some embodiments, the disclosure provides interfering nucleic acids (e.g., artificial miRNAs) targeting the huntingtin gene (HTT) and methods of treating Huntington's disease using the same.

Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a huntingtin (HTT) gene. The HTT RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of an HTT gene. The HTT RNAi agents are conjugated to an antigen binding protein that may enable subcutaneous delivery of the RNAi agents by facilitating crossing of the blood brain barrier (BBB). Pharmaceutical compositions that include one or more HTT RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described HTT RNAi agents to central nervous system (CNS) tissue, in vivo, provides for inhibition of HTT gene expression and a reduction in HTT activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including Huntington's Disease.

The present disclosure provides single- or double-stranded interfering RNA molecules (e.g., siRNA) that target a MutS Homolog 3 (MSH3) gene. The interfering RNA molecules may contain specific patterns of nucleoside modifications and internucleoside linkage modifications, as pharmaceutical compositions including the same. The siRNA molecules may be branched siRNA molecules, such as di-branched, tri-branched, or tetra-branched siRNA molecules. The disclosed siRNA molecules may further feature a 5′ phosphorus stabilizing moiety and / or a hydrophobic moiety. Additionally, the disclosure provides methods for delivering the siRNA molecule of the disclosure to the central nervous system of a subject, such as a subject identified as having Huntington's Disease.

The present invention relates to pharmaceutical compounds of Formula (I):as further described herein, and pharmaceutical compositions containing such compounds, as well as methods of using these compounds to modulate the activity of aryl hydrocarbon receptor (AhR) and to treat conditions comprising inflammation inside the intestinal tract and certain disorders of the central nervous system affected by the gut-brain axis, including IBD, ulcerative colitis, Crohn's disease, Huntington's disease, and multiple sclerosis.

The invention belongs to the technical field of molecular biology, and relates to an application of transferrin (TF) as an internal reference protein in preparation of a reagent for detecting exosome proteins of neurodegenerative diseases. The TF can maintain a stable expression level in nerve cells, brain tissues, blood plasma and serum-derived exosomes of a subject suffering from neurodegenerative diseases, including Alzheimer's disease, mild cognitive impairment, amyotrophic lateral sclerosis, Parkinson's disease or Huntington's disease, and also including neurodegenerative diseases such as Alzheimer's disease, mild cognitive impairment, amyotrophic lateral sclerosis, Parkinson's disease or Huntington's disease. The TF expression variation coefficient is obviously lower than that of a common exosome marker, and the expression level of TF has stronger correlation with the total protein amount of the exosome and is not influenced by external factors such as cell inflammation stress. The TF as the internal reference protein has more excellent performance, can help to more accurately reflect the total loading amount of the sample, and provides a more stable and reliable standardized tool for the field of exosome research.

The present invention relates to the field of diagnostics. Specifically, it relates to a method for assessing Huntington's disease of the pre-manifest stage in a subject comprising the steps of determining at least one performance parameter from a dataset of fine motoric measurements from said subject, comparing the determined at least one performance parameter to a reference, and assessing Huntington's disease of the pre-manifest stage in the subject based on said comparison. Yet, the invention contemplates a device and a system for carrying out the aforementioned methods and the use of such device or system for assessing Huntington's disease of the pre-manifest stage in the subject.

The present invention refers to an in vitro method for the diagnosis or prognosis of Huntington's disease, preferably for the early diagnosis or prognosis of Huntington's disease.

The invention discloses a 2-(piperidinyl) pyridazinone compound (I), pharmaceutically acceptable salts thereof, a preparation method of the 2-(piperidinyl) pyridazinone compound, a pharmaceutical composition of the 2-(piperidinyl) pyridazinone compound and application of the 2-(piperidinyl) pyridazinone compound in preparation of drugs for treating and / or preventing nervous system related diseases. Comprising but not limited to vascular dementia, Alzheimer's disease, frontotemporal dementia, Prion disease, dementia with Lewy bodies, Parkinson's disease, Huntington's disease, HIV-related dementia, multiple sclerosis, amyotrophic lateral sclerosis, neuropathic pain, cerebral arterial thrombosis, hemorrhagic stroke, nerve injury caused by cerebral trauma and other diseases;

A method of determining susceptibility of cancer cells to treatment with alternating electric fields, or of reducing the viability of cancer cells by applying alternating electric fields, by measuring percentage of ciliated cancer cells or by measuring average length of a primary cilia of cancer cells. A method of treating Huntington's disease by applying alternating electric fields to a brain of a subject.

The present invention relates to novel compositions comprising a self-therapeutic metal nanoparticle core coated with a hydrophilic polymer and optionally a therapeutic agent attached to the polymer. The linker includes functional groups capable of binding to the metal core and the polymer. Also disclosed is a method for treating a neurodegenerative disease in a subject, the method comprising administering to a subject suffering from a neurodegenerative disease an effective amount of a composition. The compositions exhibit self-therapeutic properties when administered to a patient with Huntington's disease. In addition, the invention comprises a method for synthesizing gold nanoparticles for the treatment of neurodegenerative diseases. The method includes coupling gold nanoparticles with polyethylene glycol (PEG) and attaching a therapeutic agent to the PEG via a linker. This enables targeted delivery of therapeutic agents to their therapeutic targets.

Described herein is a small molecule splicing modulator compound that modulates splicing of mRNA, such as pre-mRNA, encoded by genes, and methods of use of the small molecule splicing modulator compounds for modulating splicing and treating diseases and conditions.

The present disclosure relates generally to alkyne containing pharmaceutical agents, and in particular, to phenylethynyl-thiophene based compounds. More particularly, the present disclosure provides a class of compounds that can inhibit and / or attenuate apoptosis via caspase 3 for the treatment of various degenerative disorders. Additionally, the present disclosure relates to methods for treating specific degenerative disorders such as amyotrophic lateral sclerosis (ALS), Huntington's disease, epilepsy, spinal cord injury, complication due to diabetes, multiple sclerosis (MS), muscular dystrophy (MD), Parkinson's disease (PD), irritable bowel syndrome (IBS) and Alzheimer's disease (AD) in a patient comprising administering to the patient an effective amount of a present compound.

Disclosed are compounds of formula (I) wherein G1 is as antagonists of the muscarinic acetylcholine receptor M4 (mAChR M4) for use in the treatment of e.g. a neurodegenerative disorder, a movement disorder, or a brain disorder, such as e.g. Parkinson's disease, drug-induced Parkinsonism, dystonia, Tourette's syndrome, dyskinesias, schizophrenia, cognitive deficits associated with schizophrenia, excessive daytime sleepiness, attention deficit hyperactivity disorder (ADHD), Huntington's disease, chorea, cerebral palsy, and progressive supranuclear palsy. An exemplary compound is e.g. (2,5-difluoro-4-(6-(((3aR,5s,6aS)-2-((tetrahydro-2H-pyran-4-yl)methyl)octahydrocyclopenta[c]pyrrol-5-yl)amino)pyridazin-3-yl)phenyl)(imino)(methyl)-λ6-sulfanone (e.g. example 12; compound no. 7) Pharmacological data on the activity of the compounds in an mAChR M4 cell-based assay are provided (e.g. table 2).TABLE 2Human M4Cpd. No.IC50 (nM)Emin (%)*113.44239.62318.5345846575.4361883746.0385607918.43101.821186.231243.42138.63*% ACh maximum at 30 μM.

Compositions which comprise nucleic acids encoding hFAN1. Also provides are compositions comprising a nucleic acid sequence encoding artificial mirRNA molecule(s) which inhibits expression of DNA mismatch repair protein, MutS Homolog 3 (MSH3) in human subjects. Further described are uses of the nucleic acids, vectors, and compositions, provided herein for delivery of the hFAN1 coding sequence and / or miRNA in preparing a medicament and for treating a human subject having Huntington's Disease.

The present invention addresses the problem of providing an agent for preventing or treating amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), Huntington's disease (HD), spinocerebellar ataxia (SCA), aging-related degenerative or neurological disease, brain aging, or diseases associated with brain aging, as well as a more stable antibody that exhibits an effect of preventing or treating these diseases, Alzheimer's disease (AD), or frontotemporal lobar degeneration (FTLD). A human monoclonal antibody that specifically binds to human HMGB1, wherein the human monoclonal antibody (anti-human HMGB1 antibody) comprises a heavy chain CDR1, heavy chain CDR2, and heavy chain CDR3 each consisting of a specific amino acid sequence and a light chain CDR1, light chain CDR2, and light chain CDR3 each consisting of a specific amino acid sequence, is used as an agent for preventing or treating ALS, PD, HD, SCA, aging-related degenerative or neurological disease, brain aging, or diseases associated with brain aging. An antibody in which the light chain complementarity determining region (CDR) 3 of the anti-human HMGB1 antibody has been modified is used.

Compositions include CRISPR RNAs, guide RNAs, and nucleic acid molecules encoding the same. Vectors and host cells comprising the nucleic acid molecules are also provided. Further provided are RNA-guided nuclease (RGN) systems for cleaving a mutHTT allele, wherein the RGN system comprises an RNA-guided nuclease and a guide RNA. The compositions find use in cleaving or modifying a mutHTT allele, and / or modifying the expression of a mutHTT allele. The compositions are additionally useful for treating Huntington's disease (HD), particularly in an allele-specific manner.

The present description relates to a tablet formulation of 2-[3-(2,2,6,6-tetramethylpiperidin-4-yl)-3H-[1,2,3]triazolo[4,5-c]pyridazin-6-yl]-5-(2H-1,2,3-triazol-2-yl)phenol, a compound for use in treating Huntington's disease, and a method of making the same.

The invention provides a benzylimidazole glutamine cyclase inhibitor as well as a preparation method and application thereof, and belongs to the field of medical chemistry. The compound as shown in the formula I is prepared, the compound has good inhibitory activity on glutamine cyclase, and the half inhibitory concentration of most compounds reaches the nanomole level; the compound has a wide application prospect in preparation of drugs for treating Alzheimer's disease, depression, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, tumor, synovial membrane disease, gout, acute / chronic enteritis, rheumatoid arthritis or inflammatory diseases, and lays a material basis for research and development of related drugs.

The invention discloses application of bitter gourd exosomes in regulating intestinal flora. The method comprises the following steps: establishing an Alzheimer's disease mouse model, injecting the extracted balsam pear exosome into the mouse body in a gavage manner to serve as an experimental group drug, taking normal saline as a model negative control group, detecting the change of the intestinal flora of the AD mouse by applying a 16S amplicon sequencing principle, and detecting the change of the intestinal flora metabolite of the AD mouse by applying an LS-MS technology. An open field experiment, a nesting experiment and a water maze experiment are adopted to verify the treatment effect of the balsam pear exosome on AD mouse intestinal flora and metabolic level changes thereof. Results prove that the bitter gourd exosome extracted by the invention can effectively improve the intestinal flora micro-ecology of AD mice; the compound can be used for preparing a microecological preparation for regulating intestinal flora of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, different types of spinal cerebellar ataxia and the like and diseases such as cerebral apoplexy, cerebral injury, epilepsy, tumor and the like.

The invention relates to compounds, compositions, and methods for derepressing RE1 silencing transcription factor (REST) target genes are provided. In particular, a peptide having the sequence TEDLEPPEPPLPKEN (SEQ. ID NO: 1) and EDLEPPEPPLPK (SEQ. ID NO: 15), or the reversed sequences made of D-amino acids (retro inverted, RI) nekplppeppeldet (SEQ ID NO: 16) and kplppeppelde (SEQ ID NO: 17), are disclosed for inhibiting REST activity. The peptides are useful to treat, prevent, or ameliorate conditions such as traumatic brain injury, epilepsy, dementia, Huntington's Disease (HD), chronic pain, brain cancer (including glioblastoma multiforme), pancreatic cancer; diabetes, and peripheral nerve injury

The present disclosure provides methods and compositions for reducing the level of an RNA transcript produced from a mutant Huntingtin (mHtt) allele in a neuron in an individual with Huntington's disease. The present disclosure provides methods for reducing the level of an RNA transcript produced from an mHTT allele in an allele-specific manner. The present disclosure provides systems and compositions for carrying out the methods.

The present disclosure relates to the treatment of Huntington’s disease using BRD9 inhibitors.

The present invention provides compositions and methods for cleaving a mutant Huntington (mutHTT) allele. The composition comprises CRISPR RNA, guide RNA and nucleic acid molecules for coding the CRISPR RNA and the guide RNA. Vectors and host cells comprising the nucleic acid molecules are also provided. Further provided is an RNA-guided nuclease (RGN) system for cleaving mutHTT alleles, wherein the RGN system comprises an RNA-guided nuclease and a guide RNA. The compositions may be used to cleave or modify the mutHTT allele, and / or to modify the expression of the mutHTT allele. The compositions are further useful for the treatment of Huntington's Disease (HD), especially in an allele-specific manner.

This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecule compounds having a 6,6-heterocyclic structure (e.g., compounds having a naphthyridine, pyrido-pyridazine, pyrido-pyrazine, quinoline, pyrazino-pyridazine, pyrimido-pyrimidine, quinazoline, quinoxaline or cinnoline ring system) which function as inhibitors of DYRK1A, DYRK1B, DYRK2, DYRK3, CLK1, CLK2, CLK3, CLK4, CDK7, CDK8 / 19, PI3K, PDGFrA / B, mTOR, WNT, homeodomain-interacting kinases (HIPKs), and / or CMGC kinases leading to inhibition of WNT signaling, and their use as therapeutics for the treatment of Alzheimer's disease, down syndrome, Parkinson's disease, Huntington's disease, diabetes, autoimmune diseases, inflammatory disorders (e.g., airway inflammation, osteoarthritis (e.g., knee related osteoarthritis)), cancer (e.g., glioblastoma, prostate cancer, metastatic breast cancer, metastatic lung cancer, multiple myeloma, secondary metastatic tumors of the brain, colorectal cancer and metastatic colorectal cancer (e.g., metastatic colorectal cancer in the liver)), and other diseases.

The present invention provides nucleic acid molecules and methods that use miRNA sequences that knocking down mRNA for the human DNA mismatch repair protein MutS Homolog 3 (MSH3), thereby resulting in the treatment of Huntington's Disease.

The present invention addresses the problem of providing an agent for preventing or treating amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), Huntington's disease (HD), spinocerebellar ataxia (SCA), aging-related degenerative or neurological disease, brain aging, or diseases associated with brain aging, as well as a more stable antibody that exhibits an effect of preventing or treating these diseases, Alzheimer's disease (AD), or frontotemporal lobar degeneration (FTLD). A human monoclonal antibody that specifically binds to human HMGB1, wherein the human monoclonal antibody (anti-human HMGB1 antibody) comprises a heavy chain CDR1, heavy chain CDR2, and heavy chain CDR3 each consisting of a specific amino acid sequence and a light chain CDR1, light chain CDR2, and light chain CDR3 each consisting of a specific amino acid sequence, is used as an agent for preventing or treating ALS, PD, HD, SCA, aging-related degenerative or neurological disease, brain aging, or diseases associated with brain aging. An antibody in which the light chain complementarity determining region (CDR) 3 of the anti-human HMGB1 antibody has been modified is used.

Aspects of the present disclosure relate to compositions and methods useful for treating Huntington's disease. In some embodiments, the present disclosure provides interfering nucleic acids (e.g., artificial miRNAs) targeting the Huntingtin gene (HTT) and methods of using the same to treat Huntington's disease. Accordingly, in some aspects, the present disclosure provides an isolated nucleic acid comprising or encoding the sequence set forth in any one of SEQ ID NO: 1-SEQ ID NO: 22.

A cell-based screening system and method for identifying compounds that selectively modulate the expression of CAG repeat-containing RNA associated with spinocerebellar ataxias and related disorders. The system comprises a human HEK293T cell line engineered to co-express two reporter constructs: a CAG repeat-expanded polyglutamine-nanoluciferase fusion protein with at least 60 CAG repeats, and a control firefly luciferase with no CAG repeats. Each construct contains a unique probe-binding sequence downstream of the repeat region, enabling independent quantification via multiplex RT-qPCR with fluorescent probes, as well as dual luciferase assays. The cell line is optimized for high-throughput screening to identify therapeutic compounds that reduce pathogenic CAG repeat RNA levels while sparing control transcripts. The invention further encompasses methods for screening, validating, and identifying candidate therapeutics for CAG expansion disorders, including spinocerebellar ataxias and Huntington's disease.