229 results about "Huntingtons chorea" patented technology

The present disclosure provides compositions and methods useful in the treatment of trinucleotide repeat disorders, including Huntington's disease and Friedreich's ataxia. The present disclosure also provides gRNAs designed to target the HTT or FXN genes. Complexes comprising a base editor and any of the gRNAs disclosed herein are also provided by the present disclosure. The present disclosure further provides polynucleotides, vectors, cells, compositions, and kits. Methods of treating Huntington's disease and Friedreich's ataxia are also provided herein.

The disclosure provides methods for the diagnosis of Huntington's disease. In some embodiments, the method comprises detecting one or more repeat associated non-ATG (RAN) proteins in a biological sample.

The present invention relates to a method of treating a glucose-6-phosphate dehydrogenase dysregulated disorder in a subject in need thereof, the method comprising administering to the subject an effective amount of oleanolic acid, a conjugated salt thereof, or a prodrug thereof. The glucose 6-phosphate dehydrogenase dysregulated disorder can be myofibrillar myopathy, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease and Alzheimer's disease caused by BCL2 associated immortal gene mutation.

The present application relates to a sustained release delivery composition of a vesicular monoamine transporter type 2 (VMAT2) inhibitor, a deuterated derivative thereof, a pharmaceutically acceptable salt thereof, an active metabolite thereof, or a prodrug thereof for treatment of hyperkinetic movement disorders including, but not limited to, tardive dyskinesia (TD), Huntington's disease (HD) chorea, tremors, dystonia, chorea, tics, myoclonus, stereotypies, restless legs syndrome, and various other disorders with abnormal involuntary movements. The present application also relates to a sustained release delivery composition of an antipsychotic agent, a pharmaceutically acceptable salt thereof, an active metabolite thereof, or a prodrug thereof for treatment of schizophrenia, bipolar disorder, and other psychiatric diseases or disorders. The method of making or using the composition is also disclosed.

To provide 2-aminopyridine derivative compounds for use as inhibitors of nitric oxide synthase.SOLUTION: Disclosed are 2-aminopyridine derivative compounds for use as inhibitors of nitric oxide synthase (NOS). In particular, the field of the present invention relates to 2-aminopyridine derivative compounds for use as inhibitors of neuronal nitric oxide synthase (nNOS), which are formulated as pharmaceutical compositions for treating nNOS-associated diseases and disorders such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, as well as amyotrophic lateral sclerosis, cerebral palsy, stroke / ischemic brain injury, and migraine headaches.SELECTED DRAWING: Figure 1

Described herein are compounds and methods of treating or imaging a disease or disorder, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, ischemic stroke, and prion disease, comprising administering a therapeutically effective amount of a cromolyn ester.

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.

This disclosure relates to, inter alia, certain compounds, compositions, and pharmaceutical compositions thereof, that modulate the activity of the transporter protein vesicular monoamine transporter- 2 (VMAT2) and are directed to methods useful in the treatment of transporter protein vesicular monoamine transporter-2 mediated disorders, such as, neurological or psychiatric disease or disorders, including but not limited to, hyperkinetic movement disorders (e.g., tardive dyskinesia, Tourette's syndrome, Huntington's disease, tics, ataxia, chorea (such as, chorea associated with Huntington's disease), dystonia, hemifacial spasm, myoclonus, restless leg syndrome, and tremors). The disclosure further relates to synthetic methods and intermediates useful in the preparation of compounds.

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 invention features compositions and methods for treating diseases or disorders associated with undesirable neuronal excitability (e.g., de-myelinating disease, neurodegenerative disease, such as Parkinson's disease or Huntington's disease; or chronic pain, or epilepsy).

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 provides a human brain organoid drug screening platform related to Huntington's disease, and the platform comprises: (1) a first brain organoid, which is formed by differentiation culture of a visual cell line containing a plurality of CAG repetitive sequences of HTT, and (2) a second brain organoid, which is formed by differentiation culture of the visual cell line containing a plurality of CAG repetitive sequences of HTT; and (2) a second brain organoid which is formed by carrying out differentiation culture on a quantifiable cell line, wherein the quantifiable cell line contains a plurality of CAG repetitive sequences of HTT. The human brain organoid drug screening platform related to the Huntington's disease is an organoid model with a fluorescence reporter gene d2GFP and luciferase, and an enhanced synaptic active response element (E-SARE) promoter is used for marking neuron activity; in addition, secretory luciferase can detect subtle changes of neuron activity.

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.

Disclosed herein are antisense compounds and methods for selectively reducing expression of an allelic variant of a gene containing a single nucleotide polymorphism (SNP). Such methods, compounds, and composition are useful to treat, prevent, or ameliorate diseases, including neurodegenerative diseases, such as Huntington's Disease (HD).

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.