118 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.

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.

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 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.

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.

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.

Provided herein are RNAi molecules for treating Huntington's disease. Further provided herein are expression cassettes, vectors (e.g., rAAV, recombinant adenoviral, recombinant lentiviral, and recombinant HSV vectors), cells, viral particles, and pharmaceutical compositions containing the RNAi. Yet further provided herein are methods and kits related to the use of the RNAi, for example, to treat Huntington's disease.

Provided herein are compounds, pharmaceutical compositions, and methods of use for selectively reducing the amount or activity of HTT RNA comprising SNP rs7685686 in a cell or subject, and in some cases reducing the amount of mutant HTT protein in a cell or subject. Such compounds, pharmaceutical compositions, and methods of use are useful for ameliorating at least one symptom or marker of Huntington's disease.

The invention relates to the field of human genetics, more specifically neurological disorders. The invention in particular relates to the use of the antisense oligonucleotide AON1 with improved characteristics enhancing clinical applicability for treating Huntington as further defined herein.

Antibodies that bind to the HTT protein and fragments thereof are described. Methods, including compositions and methods of treatment, comprising these antibodies are also described.

The present invention relates to a compound for the prevention and / or treatment of neurodegenerative diseases. On one hand, the compound provided by the invention can effectively promote the proliferation of neuronal cells, and on the other hand, the compound has a protection effect on neuronal cell toxicity induced by neurotransmitters such as glutamic acid caused by excessive accumulation of Abeta amyloid protein, so that the effect of treating neurodegenerative diseases is comprehensively exerted; meanwhile, the compound disclosed by the invention has no obvious cytotoxicity. Therefore, the compound has a good application prospect in medicines for preventing or treating neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease and the like. Besides, a parent structure with a key active function on the neurodegenerative disease and an important influencing group in the cynanchum otophyllum extract are defined, the basic structure-function relationship between the compound and the treatment of the neurodegenerative disease is defined, and a sufficient scientific basis is provided for research and development of subsequent related drugs.

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.