35 results about "Traumatic encephalopathy" patented technology

The invention relates to anti-TDP-43 binding molecules and uses thereof. The present invention is in the field of trans-activation responsive DNA binding proteins (TARDB or also referred to as TDP-43) having a molecular weight of 43 kDa. The present invention relates to TDP-43 specific binding molecules, in particular to anti-TDP-43 antibodies or antigen binding fragments or derivatives thereof, and uses thereof. The present invention provides means and methods for diagnosing, preventing, ameliorating and / or treating diseases, disorders and / or abnormalities associated with TDP-43 aggregates, including, but not limited to, frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), chronic traumatic encephalopathy (CTE), and edge-dominant age-related TDP-43 encephalopathy (LATE).

To provide stabilization of a retromer for treating Alzheimer disease and other neurodegenerative disorders.SOLUTION: Provided is a method and a composition for increasing and stabilizing a retromer in order to treat and / or prevent Alzheimer disease and other neurodegenerative disorders. Furthermore, provided is treatment of an adenovirus base for treating Alzheimer disease (AD), and other neurodegenerative states, which are Parkinson disease (PD), neuronal ceroid lipofuscinosis (NCL), and transmissible spongiform encephalopathy (TSE or prion disease), multiple system atrophy (MSA), Down syndrome, and hereditary spastic paraplegia for example, and which are progressive supranuclear palsy (PSP), frontotemporal dementia linked to chromosomes 17q21 to 22 and subtype (FTLD-17 / FTLD-Tau) thereof, Lewy body disease (LBD), amyotrophic lateral sclerosis (AES), frontotemporal degeneration (FTD), ALS-FTD and chronic traumatic encephalopathy (CTE) for example.SELECTED DRAWING: None

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).

The present invention relates to a method of preventing and / or treating chronic traumatic encephalopathy.

Pyrazolo[1,5-a]pyrimidines are disclosed. These compounds may be useful in the treatment of neurological disorder, including frontotemporal dementia, chronic traumatic encephalopathy, Alzheimer's disease, limbic-predominant age-related TDP-43 encephalopathy, or frontotemporal lobar degeneration. Further, the invention features a method of inhibiting toxicity in a cell related to a protein TDP-43 or C9orf72. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders.

The present invention belongs to the field of transactivation-responsive DNA binding protein with a molecular weight of 43 kDa (TARDB or also known as TDP-43). The present invention relates to TDP-43 specific binding molecules, in particular anti-TDP-43 antibodies or antigen-binding fragments or derivatives thereof and their uses. The present invention provides means and methods for diagnosing, preventing, alleviating and / or treating diseases, disorders and / or abnormalities associated with TDP-43 aggregates, including but not limited to frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), chronic traumatic encephalopathy (CTE) and limbic-dominant age-related TDP-43 encephalopathy (LATE).

Diagnostic and therapeutic methods for neurodegenerative diseases. Are provided involving assaying abnormal proteins (hyperphosphorylated tau, α-synuclein, TDP-43) associated with neuronal turnover inhibition or promotion in patient samples. Abnormal protein expression and apoptotic activity are detected, aiding disease progression assessment. Therapeutically, a method is provided for treating neurodegenerative diseases, administering compounds promoting neuronal turnover or modulating proteins involved in the process. The invention extends to identifying suitable drugs, employing neuronal turnover induction, miRNA modulation, and protein activity inhibition or enhancement. The claims also encompass various species, tissues, and cultured cells. Furthermore, the invention is applicable to diverse neurodegenerative diseases with abnormal protein accumulation, presenting novel diagnostic and treatment approaches.

The invention is directed to immunological compositions of one or more peptides containing epitopes of PGN, LTA and LPS molecules that induce an immunological response in a mammal, and to multiple antibodies that bind to these epitopes. Immunological compositions and antibodies disclosed herein can be used in the treatment and / or prevention of human health disorders such as bacterial sepsis, inflammation, cancers, tumors, inflammatory diseases and disorders, and neurodegenerative disorders such as, but not limited to Alzheimer's disease, frontotemporal dementia, chronic traumatic encephalopathy (CTE), Lewy body dementia and / or limbic predominant age-related TDP-43 encephalopathy (LATE).

Provided herein are methods and compositions for treating neurological diseases (e.g., neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease, dementia, a tauopathy, chronic traumatic encephalopathy (CTE), traumatic brain injury (TBI), mild cognitive impairment); psychiatric disorders (e.g., bipolar disorder, schizophrenia, depression, anxiety, post-traumatic stress disorder, obsessive compulsive disorder); inflammation in the central nervous system) using lithium salts, activators that increase the expression or activity of the RE1 silencing transcription factor (REST), or a combination thereof, or in combination with an additional agent.

The present invention is in the field of trans-activation responsive DNA binding proteins (TARDB or also referred to as TDP-43) having a molecular weight of 43 kDa. The present invention relates to TDP-43 specific binding molecules, in particular to anti-TDP-43 antibodies or antigen binding fragments or derivatives thereof, and uses thereof. The present invention provides means and methods for diagnosing, preventing, ameliorating, and / or treating diseases, disorders, and / or abnormalities associated with TDP-43 aggregates, including, but not limited to, frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), chronic traumatic encephalopathy (CTE), and edge dominant age-related TDP-43 encephalopathy (LATE).

The invention relates to application of a gaultheria yunnanensis extract in preparation of a medicine for treating cerebral diseases, and particularly relates to application of a gaultheria yunnanensis extract in clinical treatment of Alzheimer's disease, cerebral ischemic disease, Parkinson's disease dementia, traumatic brain injury, chronic traumatic encephalopathy and other diseases. Meanwhile, the clinical disease treatment range of the gaultheria yunnanensis extract is further expanded. Particularly, the traditional Chinese medicine composition has a remarkable curative effect in clinical application of treating the Alzheimer's disease.

The invention relates to oily butylphthalide gel for treating traumatic brain injury as well as a preparation method and application of the oily butylphthalide gel. The preparation method of the oily butylphthalide gel comprises the following steps: mixing a proper amount of ethyl isobutyl sucrose ester (SAIB) and butylphthalide, adding a small amount of pure water, and violently shaking to obtain the oily butylphthalide gel. Experimental results show that the oily butylphthalide gel prepared by the method has modulus which is very matched with that of brain tissues and is beneficial to tissue regeneration. Therefore, the oily butylphthalide gel disclosed by the invention has an excellent effect of treating traumatic encephalopathy.

The present invention is in the field of transactive response DNA binding protein with a molecular weight of 43 kDa (TARDB or also TDP-43). The invention relates to TDP-43 specific binding molecules, in particular to anti-TDP-43 antibodies or antigen-binding fragments or a derivative thereof, vectors delivering nucleic acid encoding antibodies of the invention, and uses thereof. The present invention provides means and methods to diagnose, prevent, alleviate and / or treat a disease, disorder and / or abnormality associated with TDP-43 aggregates including but not limited to Frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), Chronic Traumatic Encephalopathy (CTE), and limbic-predominant age-related TDP-43 encephalopathy (LATE).

The present disclosure relates to methods and compositions for enhancing and stabilizing reverse transport complexes for the treatment and / or prevention of Alzheimer's disease and other neurodegenerative diseases. Furthermore, the present disclosure relates to use in the treatment of Alzheimer's disease (AD) and other neurodegenerative diseases such as Parkinson's disease (PD), neuronal wax-like lipofuscia deposition (NCL) and infectious cavernous encephalopathy (TSE or prion disease), multi-system atrophy (MSA), Down's syndrome and hereditary spasmodic paraplegia, as well as tau cases such as progressive suprakaryotic paralysis (PSP), the present invention relates to adenovirus-based therapies of frontotemporal dementia (FTLD-17 / FTLD-Tau), Lewy body disease (LBD), amyotrophic lateral sclerosis (ALS), frontotemporal lobe degeneration (FTD), ALS-FTD, and chronic traumatic encephalopathy (CTE) associated with chromosome 17q21-22 and subtypes thereof.

The present disclosure provides novel approaches to the treatment of Alzheimer's disease, and other neurodegenerative disorders such as chronic traumatic encephalopathy (CTE) using novel therapeutics comprising agents that reduce the interaction of a tau seed interactor with intracellular tau proteins and thus reduce or inhibit the production of tau-associated neurofibrillary tangles.

BAG3 protein is used in the treatment of, for example, is Parkinson's disease, Alzheimer's disease, Amyotrophic Lateral Sclerosis, Huntington disease, Lewy body disease, vascular dementia, mixed dementia and Traumatic Brain Injury, for example, complicated by Chronic Traumatic Encephalopathy (CTE). Therapeutically effective BAG3 compositions, BAG3 uses and BAG3 methods of treatment are described.

The present invention is in the field of AAV vectorized TDP-43 specific antibodies and uses thereof. The present invention further relates to means and methods to prevent, alleviate and / or treat a disease, disorder and / or abnormality associated with TDP-43, or TDP-43 proteinopathy, including but not limited to Frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), Chronic Traumatic Encephalopathy (CTE), and limbic-predominant age-related TDP-43 encephalopathy (LATE).

Disclosed are compounds of Formulas (I), (la), (lb), (II), (Ila), (III), (Illa), and (Illb), as well as pharmaceutical compositions thereof. The compounds can be used to improve proteostasis and enhance clearance of protein accumulation events by positively modulating the autophagy-lysosomal pathway, including augmenting the activity of cathepsin enzymes, and / or to treat neurological diseases, disorders and conditions, such as, but not limited to, Alzheimer's disease, Parkinson's disease, Huntington's disease, mild cognitive impairment, frontotemporal dementia, amyotrophic lateral sclerosis, Lewy body dementias, chronic traumatic encephalopathy, traumatic brain injury, and α-synucleinopathies.

The invention relates to butylphthalide hydrogel for treating traumatic brain injury as well as a preparation method and application of the butylphthalide hydrogel. The preparation method of the hydrogel comprises the following steps: step 1, taking a proper amount of butylphthalide injection, and adding a proper amount of multi-arm polyethylene glycol with a double-bond end group into the butylphthalide injection to form a solution containing the multi-arm polyethylene glycol with the double-bond end group and the butylphthalide; 2, taking a proper amount of butylphthalide injection, and adding a proper amount of the polysulfhydryl compound to form a solution containing the polysulfhydryl compound and butylphthalide; and step 3, mixing the solutions prepared in the step 1 and the step 2 to prepare the hydrogel. Experimental results show that the butylphthalide hydrogel prepared by the method disclosed by the invention can be continuously released in a slow-first and fast-second manner within several weeks, and the release property is matched with pathological change characteristics of traumatic brain injury. Therefore, the butylphthalide hydrogel disclosed by the invention has an excellent effect of treating traumatic encephalopathy.

The present invention is in the field of AAV vectorized TDP-43 specific antibodies and uses thereof. The present invention further relates to means and methods to prevent, alleviate and / or treat a disease, disorder and / or abnormality associated with TDP-43, or TDP-43 proteinopathy, including but not limited to Frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), Chronic Traumatic Encephalopathy (CTE), and limbic-predominant age-related TDP-43 encephalopathy (LATE).

Disclosed are compounds of Formulas (I), (Ia), (Ib), (II), (IIa), (III), (IIIa), and (IIIb), as well as pharmaceutical compositions thereof. The compounds can be used to improve proteostasis and enhance clearance of protein accumulation events by positively modulating the autophagy-lysosomal pathway, including augmenting the activity of cathepsin enzymes, and / or to treat neurological diseases, disorders and conditions, such as, but not limited to, Alzheimer's disease, Parkinson's disease, Huntington's disease, mild cognitive impairment, frontotemporal dementia, amyotrophic lateral sclerosis, Lewy body dementias, chronic traumatic encephalopathy, traumatic brain injury, and α-synucleinopathies.

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).

Provided herein are compositions and methods for treating neuroinflammatory diseases and conditions, the neuroinflammatory diseases and conditions include Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), traumatic brain injury (TBI), complex regional pain syndrome (CRPS), optic neuritis (ON), optic neuromyelitis (NMO), chronic traumatic encephalopathy (CTE), ischemic stroke (IS), vascular dementia (VAD), anti-oligodendroglia glycoprotein antibody disease (MOGAD), and the like. Transverse myelitis (TM), autoimmune encephalitis (AE), acute disseminated encephalomyelitis (ADEM), chronic meningitis (CM), central nervous system (CNS) vasculitis, hashimoto encephalitis (HE), neurosarcoidosis (NS), multi-system atrophy (MSA), migraine, chemotherapy-induced pain or dementia-related pain.

The present invention relates to dosing regimens and methods of using LY3154207, also described as 2-(2,6-dichlorophenyl)-1-[(1S,3R)-3-(hydroxymethyl)-5-(3-hydroxy-3-methylbutyl)-1-methyl-3,4-dihydroisoquinolin-2 (1H)-yllethanone, and / or pharmaceutical compositions thereof, for treatment of dopaminergic central nervous system disorders. Dopaminergic CNS disorders of the present dosing regimen methods include Parkinson's Disease, Alzheimer's Disease, Lewy body dementia (LBD), Vascular Dementia, Schizophrenia, ADHD, Depression, Autism, chronic musculoskeletal pain, fibromyalgia, cognitive impairment disorders, sleep disorders, excessive daytime sleepiness, narcolepsy, shift work disorder, traumatic brain injury, chronic traumatic encephalopathy, obesity and appetite regulation, mood disorders, lethargy, apathy, and addiction disorders.

Provided herein are artificial microRNA (miRNA) molecules for treating tauopathies. In some embodiments, the miRNA molecules target expression of Tau protein. Further provided herein are expression constructs, vectors (e.g., rAAV), cells, viral particles, and pharmaceutical compositions containing the artificial miRNA molecules. Yet further provided herein are methods and kits related to the use of the miRNA molecules, for example, to treat tauopathies including is Alzheimer's disease, progressive supranuclear palsy, corticobasal degeneration, frontotemporal dementia with parkinsonism-17, Pick's Disease, argyrophilic grain disease, globular glial tauopathy, chronic traumatic encephalopathy and post-encephalitic parkinsonism.

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.

Provided herein are methods of administering ISIS 814907 for ameliorating Alzheimer's disease, reducing Tau RNA, or reducing Tau protein in a human subject in need thereof. In certain embodiments, the Alzheimer's disease is mild Alzheimer's disease, Mild Cognitive Impairment (MCI) Due to Alzheimer's Disease, and / or Alzheimer's Disease Dementia (e.g., Mild Alzheimer's Disease Dementia). In certain instances, methods are useful for ameliorating at least one symptom or hallmark of a disease or disorder associated with Tau protein. In certain instances, the disease or disorder associated with Tau protein is a neurodegenerative disease or disorder. In certain instances, the disease or disorder associated with Tau protein is Alzheimer's disease or Fronto-temporal Dementia (FTD). In certain embodiments, the Alzheimer's disease is mild Alzheimer's disease, Mild Cognitive Impairment (MCI) Due to Alzheimer's Disease, and / or Alzheimer's Disease Dementia (e.g., Mild Alzheimer's Disease Dementia). In certain instances, the disease or disorder associated with Tau protein is a tauopathy. In certain instances, the disease or disorder associated with Tau protein is Frontotemporal Dementia with Parkinsonism-17 (FTDP-17), Progressive Supranuclear Palsy (PSP), Chronic Traumatic Encephalopathy (CTE), Corticobasal Ganglionic Degeneration (CBD), Pick Disease, Argyrophilic Grain Disease (AGD), Globular Glial Tauopathies, Epilepsy, and / or Dravet's Syndrome. Such symptoms or hallmarks include loss of memory, cognitive decline, loss of ability to understand or express speech, abnormal behavior, loss of and impaired motor function, or increase in the number and / or volume of neurofibrillary inclusions.

To provide CAR-Treg-based therapies for treating neurodegenerative diseases.SOLUTION: The invention provides compositions and methods for suppressing autoimmune components of neurodegenerative diseases, thereby providing therapeutic effects to patients suffering from such diseases. Compositions and methods include immunosuppressive moieties such as regulatory T cells (Tregs) and proteins expressed by Tregs coupled to a chimeric antigen receptor or protein that specifically binds 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.SELECTED DRAWING: None

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.