14 results about "Supranuclear palsy" patented technology

The invention provides a compound of formula (I): or a pharmaceutically acceptable salt, ester, amide or carbamate thereof, or a salt of such an ester, amide or carbamate. The invention further provides uses of the compounds of formula (I) and compositions comprising compounds of formula (I), including the use of such compounds for the detection of tau deposits, and the use of such compounds and compositions as diagnostic agents in the diagnosis or monitoring of the progression of a disease or disorder such as Alzheimer's disease, corticobasal degeneration and progressive supranuclear palsy, or for the prevention or treatment of a disease or disorder such as Alzheimer's disease, corticobasal degeneration and progressive supranuclear palsy.

Disclosed are compounds of formula (I) wherein G1 is as antagonists of the muscarinic acetylcholine receptor M4 (mAChR M4) for use in the treatment of e.g. a neurodegenerative disorder, a movement disorder, or a brain disorder, such as e.g. Parkinson's disease, drug-induced Parkinsonism, dystonia, Tourette's syndrome, dyskinesias, schizophrenia, cognitive deficits associated with schizophrenia, excessive daytime sleepiness, attention deficit hyperactivity disorder (ADHD), Huntington's disease, chorea, cerebral palsy, and progressive supranuclear palsy. An exemplary compound is e.g. (2,5-difluoro-4-(6-(((3aR,5s,6aS)-2-((tetrahydro-2H-pyran-4-yl)methyl)octahydrocyclopenta[c]pyrrol-5-yl)amino)pyridazin-3-yl)phenyl)(imino)(methyl)-λ6-sulfanone (e.g. example 12; compound no. 7) Pharmacological data on the activity of the compounds in an mAChR M4 cell-based assay are provided (e.g. table 2).TABLE 2Human M4Cpd. No.IC50 (nM)Emin (%)*113.44239.62318.5345846575.4361883746.0385607918.43101.821186.231243.42138.63*% ACh maximum at 30 μM.

The invention relates to generation, optimization and characterisation of VHH targeted against Tau MTBD (microtubule-binding domain) with high affinity, obtained by screening from a naïve synthetic library. The inventors optimized version of a lead VHH which is able to inhibit Tau aggregation in vitro and in HEK 293 aggregation-reporting cellular model, providing a new tool in Tau immunotherapies. Accordingly the invention relates to new VHH antibody that specifically binds with high affinity Tau species, especially the epitope region involved in Tau aggregation. Moreover, the inventors found that immunization with the optimized version of this lead VHH prevented the formation of neurofibrillary tangles induced by injection of extracellular h-AD in mouse model. Thus, these specific antibodies can be used for the therapy of tauopathy disorders such as Progressive supranuclear palsy (PSP).

The present invention provides compounds of formula (I), or a pharmaceutically acceptable salt, ester, or carbamate thereof, or a salt of such an ester or carbamate, wherein R 1 is OH and R 2 is H or R 1 is H and R 2 is OH. The present invention further provides uses of compounds of formula (I) and compositions comprising compounds of formula (I), including the use of such compounds for the detection of tau deposits and the use of such compounds and compositions as diagnostic agents in diagnosing or monitoring the progression of a disease or disorder such as Alzheimer's disease, progressive supranuclear palsy and corticobasal degeneration, or for the prevention or treatment of a disease or disorder such as Alzheimer's disease, progressive supranuclear palsy and corticobasal degeneration. [Formula 1] JPEG2025540931000057.jpg34152

Provided are crystalline forms of 3-(5-(4-((3,3-dimethyl-4-((1-(6-(5-(1- methylcyclopropoxy)-1H-indazol-3-yl)pyrimidin-4-yl)piperidin-4-yl)methyl)piperazin-1- yl)methyl)piperidin-1-yl)-4-fluoro-1-oxoisoindolin-2-yl)piperidine-2, 6-dione, pharmaceutical compositions comprising the crystalline form, and their use in treating conditions associated with LRRK2, such as Parkinson's disease, dementia, Progressive Supranuclear Palsy, Huntington's disease, or neuroinflammation.

Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a microtubule associated protein tau (MAPT) gene. The MAPT RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of a MAPT gene. The MAPT RNAi agents are conjugated to an antigen binding protein that may enable subcutaneous delivery of the RNAi agents by facilitating crossing of the blood brain barrier (BBB). Pharmaceutical compositions that include one or more MAPT RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described MAPT RNAi agents to central nervous system (CNS) tissue, in vivo, provides for inhibition of MAPT gene expression and a reduction in MAPT activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including Alzheimer's disease, Frontotemporal lobar degeneration dementia (FTLD), Progressive supranuclear palsy, and other tauopathies.

The invention discloses the in vitro use of a non-LTR RTE biomarker, such as LINE-1, to diagnose neurodegenerative diseases, particularly tauopathies. The diagnosis is based on identifying an increase in the number of LINE-1 copies in the biological fluids of an individual, and the difference in the number of copies of a non-LTR RTE, LINE-1, per ng of DNA in a biological sample, preferably a buffy coat, between healthy subjects (Control) and ill patients. The tauopathies are: Alzheimer's Disease (EA), Mild Cognitive Impairment (DCL), Progressive Supranuclear Palsy (PSP) / Corticobasal Syndrome (SCB) and Frontotemporal Dementia (DFT). The invention also relates to a kit comprising means for detecting the biomarker in a biological sample obtained from the individual and means for comparing the levels of the biomarker of interest in the sample with a control reference obtained from healthy individuals, and relates to an in vitro method for detecting a non-LTR RTE, such as LINE-1, in a biological sample.

Heterocyclic compounds of Formula I or Formula II or pharmaceutically acceptable salts, solvates, hydrates, tautomers or stereoisomers thereof for imaging tau protein aggregates are provided. Compounds of Formula I or Formula II may be used to detect tau protein aggregates in the diagnosis or monitoring of the progression of a disease or disorder such as Alzheimer's disease, corticobasal degeneration and progressive suprakaryotic paralysis.

Provided are RNAi agents, pharmaceutical compositions, and methods for reducing the amount or activity of PRNP RNA in a cell or a subject, and in certain instances reducing the amount of prion protein in a cell or a subject. Such RNAi agents, pharmaceutical compositions, and methods are useful to ameliorate at least one symptom or hallmark of a neurodegenerative disease. Such neurodegenerative diseases include prion diseases, such as Creutzfeldt-Jakob disease (CJD) (e.g., variant Creutzfeldt-Jakob Disease (vCJD), classic Creutzfeldt-Jakob Disease (cCJD), familial Creutzfeldt-Jakob Disease (fCJD), or sporadic Creutzfeldt-Jakob Disease (sCJD)), Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, or kuru; synucleinopathies such as Alzheimer's disease, Parkinson's disease, or dementia with Lewy bodies; or tauopathies such as frontal temporal dementia associated with a Tau mutation, Pick's disease, progressive supranuclear palsy, corticobasal neurodegeneration, or chronic traumatic encephalopathy (CTE).

The present invention provides compositions and methods for inhibiting the autoimmune component of neurodegenerative diseases and thereby providing a therapeutic effect to patients suffering from such diseases. The compositions and methods comprise immunosuppressive moieties, such as regulatory T cells (Tregs) and proteins expressed by Tregs coupled to a chimeric antigen receptor or that specifically bind to one or more glial cell markers. Therapeutically effective doses of the compounds for treating neurodegenerative diseases, including progressive supranuclear palsy (PSP), Parkinson's disease (PD), Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS), chronic traumatic encephalopathy (CTE), and prion diseases, are disclosed.

To provide a method for collecting data to evaluate the probability that a subject is afflicted with progressive supranuclear palsy.SOLUTION: The present invention provides a method that includes, in a subject-derived cerebrospinal fluid sample, measuring the amount of a first type of molecules that are bound with an antibody recognizing the KEGILQYCQEVYPELQ epitope in amyloid precursor protein and have an apparent molecular mass of 100 kDa, where the measurement data on the first type of molecules is collected as data with a positive correlation with the probability that a subject is afflicted with progressive supranuclear palsy.SELECTED DRAWING: Figure 3

To provide a biomarker correlating with the presence of progressive supranuclear palsy (PSP).SOLUTION: A method for collecting data for evaluating whether a subject may suffer from progressive supranuclear palsy, the method comprising measuring an amount of miR-6088 in a biological sample derived from the subject, the amount being collected as data that positively correlates with the possibility that the subject suffers from progressive supranuclear palsy.SELECTED DRAWING: Figure 1

The present invention provides compositions and methods for inhibiting the autoimmune component of neurodegenerative diseases and thereby providing a therapeutic effect to patients suffering from such diseases. The compositions and methods comprise immunosuppressive moieties, such as regulatory T cells (Tregs) and proteins expressed by Tregs coupled to a chimeric antigen receptor or proteins that specifically bind to one or more glial cell markers. Therapeutically effective doses of the compounds for treating neurodegenerative diseases, including progressive supranuclear palsy (PSP), Parkinson's disease (PD), Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS), chronic traumatic encephalopathy (CTE), and prion diseases, are disclosed.

The present invention is directed to activators of TMEM175 Ion Channel, which are compounds of Formulae: (AAA), (AA), (A), (I), (II), (III), (IV), (V), (VI), (B), (B-I), and (B-II). The activators described herein can be useful in the treatment of diseases or disorders associated with disfunction of TMEM175 Ion Channel, such as Neurological Disorders, Parkinson's Disease, Alzheimer's disease, dementia with Lewy bodies (DEB), multisystem atrophy (MSA), progressive supranuclear palsy (PSP). In particular, the invention is concerned with compounds and pharmaceutical compositions activating TMEM175 Ion Channel in a cell, methods of treating diseases or disorders associated with disfunction of TMEM175 Ion Channel, and methods of synthesizing these compounds.