38 results about "Tauopathy" patented technology

A method of pre-screening a human subject for a clinical trial for treatment of tauopathy or an amyloidogenic disease. The method comprises obtaining a plasma sample from the subject and determining a concentration of p217+tau present in the plasma sample. The method further comprises indicating the subject for further screening for the clinical trial when the concentration of p217+tau present in the plasma sample is greater than or equal to a minimum threshold and less than or equal to a maximum threshold. The minimum threshold corresponds to an amount of p217+tau in plasma over which subjects present with mild cognitive impairment (MCI) and an increased accumulation of tau tangles in the brain as compared to a cognitively normal patient. The maximum threshold corresponds to an amount of p217+tau present in plasma over which subjects present with pathology of widespread accumulation of tau tangles in multiple regions of the brain.

The present invention provides a tau-binding antibody or antigen-binding fragment thereof for use in a method of treating a tauopathy in a human subject in need thereof, wherein the antibody or antigen-binding fragment thereof is administered according to a particular regimen.

Binding reagents for tau protein variants, including antibodies that bind to tau protein, and uses thereof are disclosed. The uses include determining if a patient has or is at risk of developing a tauopathy, and treating a patient having a tauopathy.

BANF1, PPP2CA, and ANKLE2 were identified as genes that promote tau aggregation when disrupted. Improved tauopathy models such as cells, tissues, or animals having mutations in or inhibition of expression of BANF1 and / or PPP2CA and / or ANKLE2 are provided. Methods of using such improved tauopathy models for assessing therapeutic candidates for the treatment of a tauopathy, methods of making the improved tauopathy models, and methods of accelerating or exacerbating tau aggregation in a tauopathy model are also provided.

The present invention relates to antisense oligonucleotides capable of modulating the expression of Tau in a target cell. The oligonucleotide lines hybridize to the MAPT mRNA. The present invention further relates to conjugates of the oligonucleotides, and pharmaceutical compositions and methods for the treatment of a Tau aberrant deposition lesion (Tauopathy), Alzheimer's disease (AD), frontotemporal dementia (FTD), FTDP-17, progressive ocular nuclear paralysis (PSP), chronic traumatic brain lesion (CTE), corticobasal nuclear degeneration (CBD), epilepsy, a Display syndrome, depression, a seizure disorder (disorder of epileptic seizure), and a movement disorder (disorder of movement).

Methods of differentiating and quantifying modifications in the tau protein in bio-fluids to detect, classify, and treat a plurality of tauopathies are disclosed. The disclosed methods include liquid chromatographic mass spectrometric analyses on isolated tau protein fragments to identify and quantify deamidated or isomerized asparagines or aspartic acids indicative of a neuropathology associated with a tauopathy.

The present invention relates to antibody-based molecules that are capable of preferentially and selectively binding to the C-terminal di-phosphorylated {p}Ser396 / {p}Ser404 Tau peptide as well as to the {p}Ser404 Tau peptide and the non-phosphorylated Tau peptide, but does not bind to the {p}Ser396 Tau peptide. Such antibody-based molecules are useful to detect pathological Tau protein conformer if present in a biological sample, especially in conjunction with the diagnosis and / or treatment of Alzheimer's disease or other Tauopathy, and thus provide a diagnostic for Alzheimer's disease and other Tau pathologies. The antibody-based molecules of the present invention also have particular utility as prophylactic and therapeutic molecules for the treatment and / or prevention of Alzheimer's disease and related tauopathies.

Disclosed are methods of synthesis and / or purification of certain 3,7-diamino-phenothiazin-5-ium compounds (“diaminophenothiazinium compounds”) including Methylthioninium Chloride (MTC) (Methylene Blue), and the resulting high purity characterized by a purity greater than 98%, and very low levels of heavy metals and organic impurities Azure A, B, C and MVB. Also disclosed are methods of treatment of a tauopathy or methemoglobinemia in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the high-purity diaminophenothiazinium compound.

Methods of differentiating and quantifying modifications in the tau protein in bio-fluids to detect, classify, and treat a plurality of tauopathies are disclosed. The disclosed methods include liquid chromatographic mass spectrometric analyses on isolated tau protein fragments to identify and quantify deamidated or isomerized asparagines or aspartic acids indicative of a neuropathology associated with a tauopathy.

The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting an alpha-2A adrenergic receptor (ADRA2A) gene, as well as methods of inhibiting expression of an ADRA2A gene and methods of treating subjects having an ADRA2A-associated disease or disorder, e.g., a primary tauopathy or Alzheimer's disease, using such dsRNAi agents and compositions.

A non-invasive device for detecting Alzheimer's Disease-associated pathologies, comprising a fundus camera comprising a spectral reflectance imaging unit that includes a broadband light source and a light sensor and a lens assembly to focus light from the broadband light source onto a fundus of an eye, and one or more processors to detect reflected and / or backscattered light from the eye, illuminated by the broadband light source, using the light sensor for determining spectral reflectance information, generate a plurality of spectral reflectance maps comprising counts of reflected and / or backscattered light at a different wavelength or a different range of wavelengths, assign a weight to each of the spectral reflectance maps, and determine one or more regions of interest from the weighted spectral reflectance maps as being a potential Alzheimer's Disease-associated pathology based on a detection of one or more biomarkers indicative of Tauopathy.

This document relates to materials and methods for treating a tauopathy. For example, this document provides methods of treatment of a tauopathy that include administering a pharmaceutical preparation comprising a pharmaceutically effective amount of a compound selected from the group of staurosporine, midostaurin, and biologically active analogs thereof.

The present invention relates to a novel heteroaryl-carbohydrazone acyldinitrile compound in which a saturated heterocyclic ring is substituted or a pharmaceutically acceptable salt thereof, a method for preparing the same, and a pharmaceutical composition for preventing or treating nervous system diseases comprising the same as an active ingredient. The heteroaryl-carbohydrazone acyldinitrile compound with a substituted saturated heterocyclic ring according to the present invention can effectively inhibit the aggregation or excessive phosphorylation of Tau protein and / or TDP-43, thereby being useful in the prevention or treatment of nervous system diseases including Tau disease and TDP-43 proteopathy.

A method and positron emission tomography (PET) system for tracking the progression of tauopathy in the brain is provided. The method comprises the following steps: acquiring first PET data of a brain generated by a tau-specific radioactive tracer and second PET data acquired after the first PET data; aligning the first PET data and the second PET data with an image of the brain, the image of the brain comprising a plurality of voxels corresponding to a region of interest (ROI) within a structure of the brain; generating a first tracer uptake data set comprising tracer uptake data for each of the voxels and a second tracer uptake data set for each of the voxels; and determining the progression of tauopathies by comparing the baseline tracer uptake data and the subsequent tracer uptake data for each voxel to a progression threshold.

The present application relates to single-stranded or double-stranded interfering RNA molecules (e.g., siRNA) that target the microtubule associated protein tau (MAPT) 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 tauopathy.

The disclosure relates to formulations of double stranded ribonucleic acid (dsRNAi) agents targeting a MAPT gene, as well as methods of inhibiting expression of a MAPT gene and methods of treating subjects having a MAPT-associated neurodegenerative disease or disorder, e.g., Alzheimer's disease, FTD, PSP, or other tauopathy, using such dsRNAi agent formulations.

The present invention relates to regions within the synaptogyrin-3 RNA sequence that are targetable by oligonucleotide inhibitors, such as antisense oligonucleotides. Specifically, these synaptogyrin-3 inhibitors are provided for general pharmaceutical use and for treating or inhibiting the progression of tauopathy or the symptoms of tauopathy.

This disclosure describes, in one aspect, a method comprising administering to a subject in need thereof a pharmaceutical composition. The pharmaceutical composition comprising pharmaceutically acceptable carrier and an antigen presentation component. The antigen presentation component comprises a multivalent immunogen display vaccine format and a microtubule associated tau protein (MAPT) component linked to at least a portion of the antigen presentation component. The MAPT component comprises a sequence that is at least 90% identical to SEQ ID NO: 1; comprises no more than 30 amino acids; and comprises at least one amino acid residue modified to comprise a PO3H2 group.

Disclosed are agents that include a) a binding and / or disaggregating moiety that adheres to a target polypeptide in its amyloid fibril form, and proceed to inhibit the target protein and / or disaggregate the fibril form, and b) a nanomass moiety that promotes transfer of the agent to a site of the target polypeptide. The disclosed agents can be used in methods for destabilizing a tau amyloid fibril, and for treating a tauopathy (e.g., Alzheimer's disease, progressive supranuclear palsy) in a subject.

Provided herein is a method of identifying a pre-stage neurofibrillary tangle (NFT) in a patient sample, including obtaining a sample from a patient suspected of having or at risk of developing a tauopathy, incubating the sample with a composition comprising a first binding reagent, wherein the first binding reagent is specific to Ser262 and / or Ser356 of a tau protein, and detecting binding between the first binding reagent and the tau protein, wherein detecting binding between the first binding reagent and the tau protein indicates the presence of a pre-stage NFT in the patient sample.

To provide compounds for effective treatment of diseases and disorders related to LRRK2, which are idiopathic PD, LRRK2 mutation associated PD (e.g., PD associated with one or more LRRK2 activated mutations), primary tauopathy (e.g., progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD)), Lewy body dementia, Crohn's disease, Hansen's disease (e.g., Hansen's disease associated with type 1 inflammatory reactions), and / or neuroinflammation, for example.SOLUTION: Provided are bifunctional compounds useful as modulators of leucine-rich repeat kinase 2 (LRRK2). Particularly, the hetero-bifunctional compounds of the present disclosure contain on one end a moiety that binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds LRRK2, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The hetero-bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation / inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.SELECTED DRAWING: None

Methods of measuring the amount of singly- or multiply-phosphorylated p217+ tau protein in a sample are provided. Methods of detecting or diagnosing tauopathies, methods of determining the effectiveness of a treatment of a tauopathy, and methods of determining whether a subject is suitable for anti-p217+ tau antibody therapy are also provided. Also described are antibodies for use in the methods and kits comprising the antibodies.

The present invention provides pharmaceutical composition for the treatment of tauopathy-related diseases that can significantly improve cognitive and behavioral impairments by reducing neuronal uptake and propagation of disease-associated tau.

The present invention provides a tau-binding antibody or antigen-binding fragment thereof for use in a method of treating a tauopathy in a human subject in need thereof, the method comprising administering to the human subject at least one dose of 30 mg / kg to 120 mg / kg of the tau-binding antibody or binding fragment thereof, wherein the tau-binding antibody or binding fragment thereof comprises: a light chain variable region comprising a CDR1 selected from SEQ ID No.: 1, a CDR2 selected from SEQ ID No.: 2, and a CDR3 selected from SEQ ID No.: 3; and a heavy chain variable region comprising a CDR1 selected from SEQ ID No.: 4, a CDR2 selected from SEQ ID No.: 5, and a CDR3 selected from SEQ ID No.: 6. In various embodiments, the human subject has a low tau burden or is not an APOE4 carrier.

The present application relates to the technical field of molecular biology, and particularly relates to a deer horn stem cell exosome-derived miRNA and its use in anti-inflammatory, antioxidant, and collagen and elastin synthesis promotion. The present application performs small RNA sequencing analysis on deer horn stem cell exosomes, systematically identifies the characteristic high-abundance miRNA composition, and clearly defines the use of some specific miRNAs (such as hsa-miR-92a-3p, hsa-miR-451a, hsa-let-7b-5p, and chi-miR-191-5p) in anti-inflammatory, antioxidant, and collagen and elastin synthesis promotion, thereby providing clear and verifiable technical support for the application of the miRNAs in anti-inflammatory preparations, tissue repair materials, and functional skin care products.

Disclosed are uses of isotopically modified polyunsaturated compounds for treating, ameliorating or inhibiting the progression of a neurodegenerative disease or condition related to tauopathy in a subject in need thereof. In certain embodiments, the isotopically modified polyunsaturated compounds are deuterated polyunsaturated fatty acids or derivatives thereof.

It has been established that increased levels of lactylated of tau protein in the brain and CNS is associated with tauopathies and neurodegenerative diseases, and increased levels of lactylated lysine on tau protein has been established as a marked for AD. Compositions and methods for the detection and treatments of tauopathies have been developed. In some forms, the methods identify and quantify lactylated lysine on tau protein in a biological sample from a subject to diagnose a tauopathy, such as AD. In some forms, the methods identify a subject as having or at risk of having a tauopathy. In some forms, the methods include treating the tauopathy. Compositions to identify a tauopathy include lactylated tau binders, such as antibodies are also described. Compositions to treat or prevent a tauopathy, such as lactylated tau peptides having a defined lactyllysine, are also described.

The present invention relates to an agent for use in decreasing the level of intracellular phosphorylated tau in neurons, which agent can bind ELAVL4 with a binding affinity of at least - 8.0 kcal / mol. The agent comprises a structural element selected from the group consisting of a steroid backbone, a sugar moiety by glycosidic linkage, an O-linked glucuronide, and a lactone group and is suitably selected from the group of porphyrins, macrolactams, macrolides, vitamin D glucuronides, steroid glucuronides, withanolides, cardenolide glycosides, anthracyclines, ergoloid mesylates, ergotamines and derivates thereof, biphenyls, and piperazines. The administration of said agent leads to a decrease in protein levels of phosphorylated tau in normal neurons treated with the agent as compared to non-treated normal neurons and to a decrease in the Aβ42 / Aβ40 ratio in fAD neurons treated with the agent as compared to non-treated fAD neurons. The agent is administered for the treatment of a tauopathy, which may be involved in Alzheimer's disease, frontotemporal dementia, Parkinson's disease or progressive supranuclear palsy and multiple sclerosis.

This disclosure relates to methods for diagnosing and treating a tauopathy, e.g., Alzheimer's disease, in a subject, the methods comprising, in part, identifying one or more post-translation modifications (PTMs) in the subject.

The present disclosure provides monoclonal antibodies that selectively bind to pathological tau over native tau. In certain aspects, the antibodies inhibit or minimize propagation of tau aggregates and / or reduce spread of pathological tau in vivo. In other aspects, the disclosure comprises a method of treating, ameliorating, and / or preventing a tauopathy in a subject, comprising administering any one of the antibodies of the disclosure to the subject. In yet other aspects, the disclosure comprises methods of detecting pathological tau using any one of the antibodies of the disclosure.