210 results about "Huntingtin" patented technology

Among other things, the present disclosure provides various technologies including chirally controlled oligonucleotide compositions and technologies tor 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, tire present disclosure provides technologies useful 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.

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.

Described herein are crystalline forms of 6-(6-(((1R,2R,3S,5S)-2-fluoro-9-azabicyclo[3.3.1]nonan-3-yl)(methyl)amino)pyridazin-3-yl)-2-methylbenzo[d]oxazol-5-ol (compound A), a small molecule splicing modulator (SMSM) of mRNA, such as pre-mRNA, encoded by genes, for the treatment of Huntington's disease.

The BAG3 proteins are useful in the treatment of Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, Lewy body disease, vascular dementia, mixed dementia and traumatic brain injury, such as chronic traumatic encephalopathy (CTE). A therapeutic BAG3 composition, use of BAG3, and a method of treatment of BAG3 are described.

Described herein is 6-(6-(((lR,2R,3S,5S)-2-fluoro-9- aza bicyclo[ 3.3.1 ]nonan-3-y l)(methyl)a mino) pyridazin-3-y l)-2- methylbenzo[d]oxazol-5-ol (structure B) as a small molecule splicing modulator (SMSM) of mRNA, such as pre-mRNA, encoded by genes, for the treatment of neurological and neurodegenerative diseases, such as e.g. Huntigton's disease, and brain cancer.

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 invention includes compositions and methods of treating CNS-related conditions, comprising: administering an effective amount of a compound that lowers the levels of one or more branched-chain amino acids (BCAAs) or metabolites thereof, or any pharmaceutically acceptable salt thereof, wherein the CNS-related conditions is selected from the group consisting of Alzheimer's disease and any related forms of dementia including vascular dementia, Lewy body dementia, frontotemporal dementia, Creutzfeldt-Jacob disease, Wernicke-Korsakoff disease, and Huntington's disease, Multiple sclerosis, Parkinson's disease, autism, Amyotrophic lateral sclerosis (ALS), Hereditary diffuse leukoencephalopathy with spheroids (HDLS) and epilepsy.

Aspects of the present disclosure relate to compositions and methods useful for the treatment of nervous system diseases and disorders. In some embodiments, the disclosure provides methods of treating a nervous system disease or disorder comprising administering both a viral vector comprising an interfering nucleic acid (e.g., an artificial miRNA) and a viral vector comprising a CYP46A1 protein. In some embodiments, the disclosure provides methods of treating Huntington's disease comprising administering both a viral vector comprising an interfering nucleic acid (e.g., an artificial miRNA) targeting the Huntington's gene (HTT) and a viral vector comprising a CYP46A1 protein. In some embodiments, the viral vector comprises a modified viral capsid, for example, for preferentially targeting cells in the CNS or PNS.

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.

A composition for treating Huntington's disease (HD) by reducing endogenous Huntingtin (HTT) levels in a target includes a siRNA including a siRNA sequence selected from SEQ ID NOs:47 to 149, and a carrier peptide comprising a peptide sequence of SEQ ID NO:1. The carrier peptide may target the nicotinic acetylcholine receptor (nAChR) of neuronal cells in order to deliver the siRNA across the blood-brain barrier (BBB). In some embodiments, the siRNA may be conjugated with the carrier peptide. A method of reducing endogenous HTT levels to treat HD in the target may include administering a composition including a siRNA sequence selected from SEQ ID NOs: 47 to 149 to the target.

The invention relates to neurodegenerative disorders, and particularly to diagnostic and prognostic methods, apparatus and kits for neurodegenerative disorders, such as mild cognitive impairment (MCI), Alzheimer's disease, Parkinson's disease, Huntington's disease or Motor Neurone disease. The invention also extends to methods of detecting novel biomarkers, and methods for treating patients diagnosed or prognosed with a neurodegenerative disorder. A mathematical correlation between the concentrations of Tau protein and T14 peptide is found in samples from healthy subjects without a mood disorder, but not in samples from subjects having neurodegenerative disorders or a predisposition thereto.

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.

The present invention relates to compounds, compositions and methods for deinhibiting a RE1 silencing transcription factor (REST) target gene. In particular, disclosed is a peptide having the sequences TEDLEPPEPPLPKEN (SEQ ID NO: 1) and EDLEPPEPPLPK (SEQ ID NO: 15) or a reverse sequence (reverse inversion, RI) consisting of D-amino acids nekplppeppeldet (SEQ ID NO: 16) and kplppeppelde (SEQ ID NO: 17), for use in the inhibition of REST activity. The peptides can be used for treating, preventing or alleviating diseases 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 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 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 disclosure provides single-stranded or double-stranded interfering RNA molecules (e.g., siRNAs) that target the Huntington (HTT) gene. The interfering RNA molecule may contain a specific pattern of nucleoside modification and inter-nucleoside linkage modification as a pharmaceutical composition comprising the interfering RNA molecule. The siRNA molecule may be a branched siRNA molecule, such as a two-branched, three-branched or four-branched siRNA molecule. The disclosed siRNA molecules may also be characterized by a 5 '-phosphorus stabilizing moiety and / or a hydrophobic moiety. In addition, the present disclosure provides methods for delivering siRNA molecules of the present disclosure to a subject, such as the central nervous system of a subject identified as having Huntington's disease.

The present disclosure relates to transcription modulator molecules having a first terminus, a second terminus, and an oligomeric backbone and methods for treating Huntington's disease (HD).

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 present invention relates to a method for the quantification of seeding (Δt50) of an amyloidogenic aggregate, methods for assessing the risk for development, predicting the onset or assessing the progression of a polyQ disease, and a method for identifying compounds that inhibit mHTT seeding activity (HSA) in vitro. Further, uses of fluorophore-bearing polyQ proteins, particularly mutant N-terminal huntingtin fragments comprising exon-1 and related soluble protein constructs are provided.

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.

[Problem] To provide a prophylactic or therapeutic agent for amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), Huntington's disease (HD), cerebellar ataxia (SCA), degenerative diseases associated with aging or neurological diseases, brain aging, or diseases associated with brain aging, alzheimer's disease (AD), frontotemporal lobe degeneration (FTLD) and an antibody having a higher stability and exhibiting a prophylactic or therapeutic effect. A human monoclonal antibody (anti-human HMGB1 antibody) that specifically binds to human HMGB1 is used as a prophylactic or therapeutic agent for ALS, PD, HD, SCA, degenerative diseases associated with aging, neurological diseases, brain aging, or diseases associated with brain aging, said human monoclonal antibody comprising: a heavy chain CDR1, a heavy chain CDR2, and a heavy chain CDR3 each comprising a specific amino acid sequence; and a light chain CDR1, a light chain CDR2, and a light chain CDR3 comprising a specific amino acid sequence. An antibody in which the light chain complementarity determining region (CDR) 3 of the anti-human HMGB1 antibody has been modified is used.

A fusion molecule having phagocytosis-inducing activity is disclosed. The fusion molecule contains a first region capable of binding a TAM receptor and a second region capable of binding to a target substance of which aberrant accumulation is associated with or characteristic of diseases. The fusion molecule effectively clears and / or reduces and / or suppresses accumulated abnormal proteins, such as beta-amyloid, tau, alpha-synuclein, huntingtin, or prion, or the like. Uses of the fusion molecule are disclosed. The fusion molecule can be used for prevention or treatment of proteinosis caused by the abnormal accumulation of substances.

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.

Disclosed herein are methods of treating central nervous system diseases, such as Alzheimer's disease and Huntington's disease, using lipophilic siRNA conjugates that can bind to albumin. The disclosed methods can advantageously provide widespread, long-term gene silencing in the central nervous system. An example method includes administering to a subject an effective amount of a conjugate, optionally in combination with a pharmaceutically acceptable excipient, wherein the conjugate includes a siRNA capable of inhibiting expression of a protein associated with the central nervous system disease; a lipophilic ligand capable of binding albumin; and a linker attaching the siRNA to the lipophilic ligand, the linker including a branching molecule attached to the siRNA, and a hydrophilic spacer attaching the branching molecule to the lipophilic ligand.