67 results about "Tauopathy" patented technology

The present invention is a composition and method for the prevention and treatment of a tauopathy. The composition of the invention includes N-terminal amino acid residues of the tau protein, which have been identified as being involved in toxic activation of a PP1 / GSK3 signaling cascade and inhibition of fast axonal transport in human tauopathies.

The present invention provides a method for the diagnosis of tauopathies in an individual and / or for the differential diagnosis of a tauopathy versus a non-tauopathy based on the detection of the ratio of phospho-tau (181) / total tau in said individual. The present invention further provides a phospho-peptide for standardization in a method of the invention.

This invention concerns affinity tools for oligomeric forms of tau protein. It relates to the field of neurodegeneration, more particularly to the field of tau-related diseases and tauopathy. The invention provides novel tau antibodies and antibody fragments, nucleic acids encoding such antibodies and antibody fragments, cell lines producing such antibodies and antibody fragments, antibody compositions, and kits for the detection of aggregated tau and for the diagnosis of diseases involving aggregated tau. The invention further provides methods for the detection of aggregated tau, for the diagnosis of diseases involving aggregated tau, and for the identification of compositions interfering with the formation and / or stability of tau aggregates.

A method for determining the Braak stage of neurofibrillary degeneration associated with a tauopathy in a subject having neurofibrillary degeneration is disclosed. The method comprises the steps of (i) administering to the subject a conjugated, chelated or detectable chemical group-associated ligand that labels aggregated paired helical filament (PHF) tau protein and is capable of crossing the blood brain barrier; (ii) determining the presence and\or amount of ligand bound to extracellular aggregated PHF tau in the medial temporal lobe of the brain of the subject, and (iii) correlating the result of the determination made in (ii) with the extent of neurofibrillary degeneration in the subject. Preferred ligands include sulphonated-benzothiazole-like compounds and diamonophenothiazines.

Provided herein is an isolated antibody or antigen-binding fragment that specifically binds tau, the antibody or fragment comprising a heavy chain variable (VH) region and a light chain variable (VL) region having amino acid sequences set forth herein. Also provided are methods of preventing or treating a tauopathy in a subject, comprising administering to a human in need of therapy for a tauopathy with one or more antibodies or fragments as described herein, wherein the antibodies or antigen-binding fragment are administered under conditions and in an amount effective to prevent or treat the tauopathy.

The application relates to an immoalditol compound for selectively inhibiting glycosidases, a prodrug thereof and a pharmaceutical composition comprising the compound or the prodrug The application also relates to the use of the immoalditol compound for treating diseases and disorders related to deficiency or overexpression of O-GlcNAcase, accumulation or deficiency of O-GlcNAc Such diseases and disorders include neurodegenerative diseases, tauopathy, cancers, and cardiac disorders

This invention concerns affinity tools for oligomeric forms of tau protein. It relates to the field of neurodegeneration, more particularly to the field of tau-related diseases and tauopathy. The invention provides novel tau antibodies and antibody fragments, nucleic acids encoding such antibodies and antibody fragments, cell lines producing such antibodies and antibody fragments, antibody compositions, and kits for the detection of aggregated tau and for the diagnosis of diseases involving aggregated tau. The invention further provides methods for the detection of aggregated tau, for the diagnosis of diseases involving aggregated tau, and for the identification of compositions interfering with the formation and / or stability of tau aggregates.

This invention provides compounds, compositions, and methods for treating a disorder selected from cancer, hyperinsulinemia, hypoglycemia, hyperinsulinemia with hypoglycemia, atypical Parkinson's disease, Huntington's disease, multiple systems atrophy, GM3 synthase deficiency, GM2 synthase deficiency or tauopathy.

The present invention provides methods of proteolytically converting a precursor protein (e.g. tau) to a product fragment (e.g., a 12 kd fragment) in a stable cell line, wherein the precursor protein is associated with a disease state in which the precursor protein aggregates pathologically (e.g. a tauopathy), and the methods comprise: (a) providing a stable cell line transfected with nucleic acid encoding: (i) a template fragment of the precursor protein such that the template fragment is constitutively expressed in the cell at a level which is not toxic to the cell; and (ii) the precursor protein, which protein is inducibly expressed in the cell in response to a stimulus, whereby interaction of the template fragment with the precursor protein causes a conformational change in the precursor protein such as to cause aggregation and proteolytic processing of the precursor protein to the product fragment. The method is preferably used to screen for modulators of the aggregation process by monitoring production (or modulation of production) of the product band or bands. Also provided are materials for used in the assays, plus medicaments, and related uses and processes, based on compounds which show high activity in the assay of the invention e.g. reduced diaminophenothiazines.

An antibody binding to Tau, phosphorylated at serine 422 (pS422), characterized in specifically binding to phosphorylated Tau fragment of SEQ ID NO: 9 and to Tau pS422, but not binding to Tau and to phosphorylated MCAK fragment of SEQ ID NO: 17 is useful in the treatment of a Tauopathy.

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 quantitative methods for the detection of tau protein and / or tau fragments. More specifically, the present invention provides quantitative methods for diagnosing a tauopathy or ruling out a tauopathy as the cause of disease, particularly the diagnosis and ruling of Alzheimer's disease. The present invention further provides a method for diagnosing a tauopathy by computing the ratio of two detected tau proteins or tau fragments.

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.

A method of diagnosing or assessing risk of a tauopathy in a person is disclosed. The method may comprise collecting a nasal sample of exhaled breath from the person's nose, analyzing the nasal sample to detect the presence of tau protein in the sample, and determining the concentration of tau protein in the nasal sample, wherein the tau protein concentration in the nasal sample indicates susceptibility to the tauopathy.

An object of the present invention is to provide a probe for imaging a β-sheet structure protein which can be used for the diagnosis of conformational diseases, particularly disease (tauopathy) having a cardinal symptom such as intracerebral accumulation of tau protein, for example, Alzheimer's disease. Another object of the present invention is to provide a compound which is highly specific to tau and can image tau with satisfactory sensitivity, and also has high brain transition, low or non-recognized bone-seeking properties and low or non-recognized toxicity.According to the present invention, the above problems are solved by providing a compound of a formula I (wherein A, R1, R2, R3, R4, R5, R6, Ra and Rb are as defined in the present description) or a pharmaceutically acceptable salt or solvate thereof.

Methods of diagnosing a tauopathy and predicting whether a subject will develop a tauopathy are provided. Also provided are antibody preparations that specifically bind to tau phosphorylated at tyr394 and / or tyr310. Methods of inhibiting tau phosphorylation in a cell and methods of treating a subject having a tauopathy are additionally provided. Methods of treating a subject at risk for a tauopathy are also provided. Additionally, non-human mammals comprising a transgene encoding an abl tyrosine kinase are provided. Also provided are methods of evaluating whether a compound inhibits development of a tauopathy.

The present invention provides a therapeutic treatment for a neurodegenerative disease with a pan-PPAR agonist, such as bezafibrate. In particular, the present invention provides that pan-PPAR agonists enhance PPAR related responses in both the central nervous system and peripheral tissues in Huntington's Disease (HD) and tauopathy. Therapeutic compositions comprising one or more pan-PPAR agonist(s), and kit thereof, for treating a neurodegenerative disease or disorder are also provided.

The present invention relates to a novel method for the treatment and / or prophylaxis of a tau-mediated neurodegenerative disease and / or of a tau-mediated neurodegenerative pathological condition, especially of a neurodegenerative disease and / or of a neurodegenerative pathological condition associated with and / or accompanied by tau aggregation, and in particular for the treatment and / or prophylaxis of a tauopathy; compounds and / or agents and compositions for such treatment and / or prophylaxis, and the manufacture of the compounds and / or agents and compositions suitable for the said treatment and / or prophylaxis. In this regard, the present invention relates especially to the use of compounds acting as PERK activator, a prodrug thereof, a derivative thereof and / or a pharmaceutically acceptable salt of any thereof, as a medicament. In contrast to the prior art which addresses mainly PERK inhibition, or occasionally only the apoptotic arm of PERK of activation, the present invention pertains to the effects of indirect or direct PERK activation achieved via the neuroprotective arm of PERK signaling.

Methods of evaluating a compound for the ability to reduce a mental defect in a metazoan are provided, where the mental defect is caused by Fragile X syndrome, a tauopathy, Huntington's disease, neurofibromatosis 1, Parkinson's disease. The methods comprise determining whether the compound reduces a mental effect of the analogous disease in a Drosophila melanogaster Also provided are methods of evaluating a compound for the ability to improve learning or memory in a mammal. The methods comprise determining whether the compound improves learning or memory in a Drosophila melanogaster that is deficient in a dFRM1. Additionally, methods of treatment of a mammal deficient in expression of an FMR1 gene are provided. The methods comprise treating the mammal with a compound in a pharmaceutically acceptable excipient, where the compound inhibits expression or activity of a group II or group I metabotropic glutamate receptor (mGluR), an inositol trisphosphate receptor (InsP3R), a glycogen synthase kinase-3β (GSK-3β), or a phosphodiesterase-4 (PDE-4) in the mammal.

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.

The present invention is a composition and method for the prevention and treatment of a tauopathy. The composition of the invention includes N-terminal amino acid residues of the tau protein, which have been identified as being involved in toxic activation of a PP1 / GSK3 signaling cascade and inhibition of fast axonal transport in human tauopathies.

Disclosed are compounds of formula (1)-(V): where the substituents are as provided herein. Further disclosed are methods of inhibiting tau aggregation, treating or ameliorating a tauopathy or cancer by administration of such a compound. Tau is a microtubule-binding protein that accumulates in a number of neurodegenerative disorders, including frontotemporal dementia and Alzheimer's disease (AD). The presence of abnormal tau correlates with neuron loss and memory deficits in patients with AD and other neurodegenerative disorders that involve tau accumulation.

The present invention relates to antibody-based probes (including single domain antibody fragment, scFv molecules, antibodies, antibody fragments, diabodies, and the epitope-binding domains thereof) that are capable of immunospecifically and selectively binding to a phospho-serine-containing epitope of Tau, such as, for example, Tau-phospho-serine 396 / 404 peptide. Such imaging ligands are useful to detect pathological Tau protein conformer if present in a biological sample, especially in conjunction with the diagnosis of Alzheimer's disease or other tauopathy, and thus provide a diagnostic for Alzheimer's disease and other Tau pathologies. The scFv molecules of the present invention have utility as diagnostic markers for, Alzheimer's disease and related tauopathies and as pharmaceutical compositions for the treatment of such conditions.

The present invention addresses the problem of providing an agent and a method for suppressing the progression of tauopathy such as Alzheimer-type dementia. 1-(3-(2-(1-benzothiophen-5-yl)ethoxy)propyl)azetidin-3-ol or a salt thereof has an effect of decreasing the level of phosphorylated tau protein and on decreasing the level of amyloid-beta protein in the brain parenchyma, and is useful as a prophylactic or therapeutic agent for tauopathy. Thus, it is possible to prevent or treat tauopathy by administering 1-(3-(2-(1-benzothiophen-5-yl)ethoxy)propyl)azetidin-3-ol or a salt thereof.

The present invention provides a method of treating or ameliorating a neurodegenerative disease in a mammal, the method comprising administering to the mammal a therapeutically effective amount of a neurodegenerative disease drug, wherein the drug is a substrate of an ABC transporter inhibitor, wherein the mammal is further administered a therapeutically effective amount of an ABC transporter inhibitor, whereby the neurodegenerative disease is treated in the mammal. In certain embodiments, the neurodegenerative disease comprises at least one selected from the group consisting of spinal cord injury, Alzheimer's disease, Parkinson's disease, Huntington's disease, prion disease, amyotrophic lateral sclerosis, a tauopathy, and chronic traumatic encephalopathy.