81 results about "Huntingtin" 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.

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 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.

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, 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 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.

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 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 invention is in the field of genetic editing tools and methods of genetic endineering. It relates to the engineering of rare-cutting endonucleases designed to contract highly repetitive motives in chromosomes, which are at the origin of certain genetic diseases, in particular the so-called "triplet repeat diseases", such as the Huntington disease. The invention encompasses the method for contracting the repetitive motives, the rare-cutting endonucleases for use to contract repetitive motives in a gene subjected to repeat disorder, the polynucleotides and vectors encoding thereof as well as the resulting pharmaceutical compositions.

The present invention provides small molecule drugs and pharmaceutical compositions for the treatment and prevention of diseases related to the formation of certain types of oligomers in a subject. More specifically, the drugs and compositions reduce or prevent the formation of oligomers formed from tau protein, TDP-43, Huntingtin's protein and / or alpha-synuclein. It further provides a method of reducing formation of or disrupting TDP-43, alpha-synuclein, Huntingtin's protein and / or tau protein oligomers in a subject, the method comprising the step of administering to the subject in need thereof a therapeutically effective amount of a pharmaceutical composition.

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.

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.

The present disclosure provides compounds, compositions, and / or methods for treating, preventing, inhibiting, amelio-rating, or delaying the onset of Huntington's disease and / or a HTT proteinopathy in a subject. The methods can comprise 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-2,6-dimethylphenyl)-1-oxopropan-2-yl)-5- guanidinopentanamide, or a pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, and / or solvate thereof, alone or in combination with one or more other therapeutic agents.

The invention relates to a plasmid vector for detecting the translation condition of amino acid sequence protein and application of the plasmid vector, and belongs to the technical field of biology. The plasmid vector for detecting the protein translation condition of the amino acid sequence, provided by the invention, is loaded with an exogenous amino acid sequence, and the amino acid sequence contains an amino acid repetitive sequence; a fluorescent protein coding gene of one color is inserted in the upstream of an amino acid repetitive sequence coding region, and a fluorescent protein coding gene of another color is inserted in the downstream of the amino acid repetitive sequence coding region. According to the invention, the translation process of the protein containing the amino acid repetitive sequence in the cell can be monitored in real time according to the expression condition of the fluorescent protein, and the formation process of the truncated object after translation blocking is captured in real time, so that a favorable tool is provided for researching and evaluating the translation condition of the protein containing the amino acid repetitive sequence in the cell; the method can also be further applied to pathogenesis research of related diseases such as Huntington's disease and / or neuronal intracellular inclusion body disease.

The present invention relates to the use of a combination of vitamins, more specifically to the combined use of biotin and thiamine, for the treatment of Huntington's disease. More specifically, the present invention explains that treatment with a combination of biotin and thiamine can improve the neurological, neuroimaging and spectroscopic symptoms associated with Huntington's disease.

The present invention relates to some crystal forms for a cinnamic compound, BMX, which is an inhibitor of histone deacetylase (HDAC), useful as an agent for the prevention or treatment of diseases associated with HDAC, including for treating tumor or cell proliferative diseases, diabetes mellitus, or neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, Spinocerebellar Ataxias (SCA) and human spinal muscular atrophy (SMA). Also provided are a method for preparing the crystal forms and pharmaceutical compositions comprising the crystal forms.

The invention discloses a combined cell transplantation system for Huntington's disease treatment, a preparation method and application. The invention belongs to the technical field of biomedicine, and aims at solving the problems that when an existing stem cell transplantation technology is used for treating the Huntington's disease (HD), the graft survival rate is low, differentiation uncertainty is high, and integration with a host neural network is difficult. The combined cell transplantation system for treating the Huntington's disease comprises human umbilical cord mesenchymal stromal cells (hUC-MSCs) and striatum organoid (hStrOs), the human umbilical cord mesenchymal stromal cells play a role in immunoregulation and provide endogenous immune microenvironment support, and the human umbilical cord mesenchymal stromal cells play a role in immunoregulation and provide endogenous immune microenvironment support; the striatum organ takes medium spinous projective neurons (MSNs) for expressing DARPP-32 and CTIP-2 as a main body, and undertakes a cell replacement function. The HD cell therapy is promoted to be converted from a traditional single cell replacement mode to an'immune regulation-nerve regeneration 'multi-dimensional functional remodeling mode through cooperation of the HD cell therapy and the Huntington's disease, and a new way is provided for cell therapy of the Huntington's disease.

The invention relates to a single domain antibody that binds Heparin-binding EGF-like growth factor (HB-EGF) for use in preventing, treating and / or diagnosing e.g. a brain disease, wherein the single domain antibody is in combination with a therapeutic compound and / or a diagnostic / imaging compound. The single domain antibody may in particular be a Variable domain of a Heavy chain only (VHH) antibody of camelid origin or an engineered single-domain antibody (sdAb) of other mammalian and be capable of transporting cargo such as peptides or other molecules into the brain across the blood-brain barrier (BBB) by receptor-mediated transcytosis (RMT). The brain disease may for example be Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, brain tumor, or Hunter syndrome.

The present invention relates to the field of biotechnology and the use of chemically modified antisense oligonucleotides (AONs) for the deamination of one or more target adenosines in the transcript of (mutant) human Huntingtin (HTT) for use in the treatment, prevention, or delay of Huntington's disease (HD). In particular, the target adenosines are in the GAU codon coding for aspartic acid at position 572 that is part of a caspase-1 proteolytic cleavage site in the human HTT protein, and / or in the GAC codon coding for aspartic acid at position 586 that is part of a caspase-6 proteolytic cleavage site in the human HTT protein.