152 results about "Huntingtin" 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.

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.

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.

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.

Disclosed are compositions and / or methods of use of the compositions for patients with neuronal diseases such as AD, Parkinson's, Huntington's, multiple sclerosis, and ALS. In certain embodiments flavonoids alone, or in a pharmaceutical preparation, are administered through the nasal olfactory route. In certain embodiments the flavonoid is apigenin and the neural disease is Alzheimer's. In some embodiments a porosome complex is administered for reconstitution into a neural cell. In certain embodiments, a co-administered blood-brain barrier traversing peptide is configured as a mimic of a domain of ATP 1 A3 and / or Tubulin.

The present disclosure provides compounds, compositions and / or methods for treating, preventing, inhibiting, ameliorating, or delaying the onset of Huntington's disease and / or HTT proteinopathy in a subject. The methods may include administering to the subject an effective amount of a peptidomimetic compound, such as (R)-2-amino-N-((S)-1-(((S)-5-amino-1-(3-benzyl-1, 2, 4-oxadiazol-5-yl) pentyl) amino)-3-(4-hydroxy-2, 3, 4-triazole-3-yl)-3-(4-hydroxyl-2, 3, 4-triazole-3-yl)-3-(4-hydroxyl-2, 3, 4-triazole-3-yl)-3-(4-hydroxyl-2, 3, 4-triazole-3-yl)-3-(4- The present invention relates to a pharmaceutical composition, in particular, a pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate and / or solvate thereof, or a pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate and / or solvate thereof.

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).

The present disclosure provides, among other things, a variety of techniques, including chirally controlled oligonucleotide compositions, and techniques for making and using such oligonucleotide compositions. In some embodiments, the present disclosure provides techniques useful for allele-specific knock-down of a mutant Huntingtin transcript. In some embodiments, the present disclosure provides techniques useful for reducing the expression, level, amount, and / or activity of a mutant Huntingtin transcript or product thereof. In some embodiments, the present disclosure provides methods for treating Huntington's disease.

The invention provides a composition containing a phosphodiesterase 5 inhibitor (PDE5 inhibitor) and an acetylcholin esterase inhibitor (AChEI) for preventing or treating neurodegenerative diseases and a use method of the composition. Wherein the PDE5 inhibitor is selected from the group consisting of mironafil, sildenafil, vardenafil, tadalafil, udenafil, dabigatafil, avanafil, and pharmaceutically acceptable salts, solvates, hydrates and mixtures thereof; and the AchEI is selected from the group consisting of donepezil, rivastigmine, galanthamine, poison hyacinth alkali, tacrine, metriofonate, phenylserine, tolserine, eosin, huperzine A and huperzine B, galangin, anacardol, donepezine-AP2238, donepezil-tacrine, tacrine-ferulic acid hybrids, tacrine-hydroxyquinoline, ladotegil, an indenyl derivative thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable salt thereof. Pharmaceutically acceptable salts, solvates, hydrates, and mixtures; and the neurodegenerative disease is dementia, Parkinson's Disease (PD), Alzheimer's Disease (AD), Huntington's Disease (HD), or Multiple Sclerosis (MS).

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 identification of a direct kinase of eukaryotic initiation factor 2 alpha (eIF2α), microtubule affinity-regulating kinase 2 (MARK2), which phosphorylates eIF2α in response to proteotoxic stress, is provided. Inhibitors of MARK2 and their use in treating neurodegenerative disease, including Alzheimer's disease, Parkinson disease, Creutzfeldt-Jakob disease, Huntington's disease, frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), also are disclosed.