55 results about "Lewy body" patented technology

Disclosed is a method of treating a neurodegenerative disease such as Parkinson's disease, diffuse Lewy body disease, transitional Lewy body dementia, and multiple system atrophy in a subject. The method comprises administering to the subject a therapeutically effective amount of a peptide comprising an α-synuclein binding domain operably linked to a protein transduction domain and a proteasomal targeting domain, wherein the α-synuclein binding domain is derived from a reversed sequence of β-synuclein. Other methods, as well as uses and compositions, are disclosed.

The invention discloses a 2-(piperidinyl) pyridazinone compound (I), pharmaceutically acceptable salts thereof, a preparation method of the 2-(piperidinyl) pyridazinone compound, a pharmaceutical composition of the 2-(piperidinyl) pyridazinone compound and application of the 2-(piperidinyl) pyridazinone compound in preparation of drugs for treating and / or preventing nervous system related diseases. Comprising but not limited to vascular dementia, Alzheimer's disease, frontotemporal dementia, Prion disease, dementia with Lewy bodies, Parkinson's disease, Huntington's disease, HIV-related dementia, multiple sclerosis, amyotrophic lateral sclerosis, neuropathic pain, cerebral arterial thrombosis, hemorrhagic stroke, nerve injury caused by cerebral trauma and other diseases;

Combination compositions of Compound 1 and fesoterodine for use in the treatment of neurological disorders, such as schizophrenia, Alzheimer's disease psychosis, Parkinson's disease psychosis, cognitive in Alzheimer's disease, psychosis in Lewy body dementia, bipolar disorder, and dyskinesia, are described.

The present invention provides an antibody or a conjugated fragment of a citrulline-containing epitope used for the treatment or prevention of diseases associated with the release of extracellular traps from cells, such as neutrophil extracellular trap (NET)-associated pathology (NET-associated pathology) or eosinophil extracellular trap (EET)-associated pathology (EET-associated pathology), and provides a method comprising administering at least one dose of the antibody at a specific concentration. The present invention also provides the method itself. NET-related pathologies include systemic lupus erythematosus (SLE), lupus, sepsis, vasculitis, inflammatory arthritis, rheumatoid arthritis and osteoarthritis, psoriasis, Alzheimer's disease, autoimmune hepatitis, juvenile idiopathic arthritis, myositis (polymyositis and dermatomyositis), Sjögren's disease, antiphospholipid syndrome, Behçet's disease, spondylitis, spondyloarthritis, multiple system atrophy, Parkinson's disease, Lewy body dementia, asthma, allergic rhinovirus exacerbated asthma, allergic asthma, acute respiratory distress syndrome, cystic fibrosis, fibrosis and idiopathic pulmonary fibrosis, heart failure, atherosclerosis, dry eye disease, uveitis, non-granulomatous uveitis, granulomatous uveitis, dermatitis, atopic dermatitis, COPD, bronchitis, or wound healing in diabetes, cancer, cancer metastasis, or wound healing in diabetes, cancer, cancer metastasis, and in This includes other NET-related pathologies, such as the health of transplanted organs in vivo or ex vivo.The present invention also relates to wound healing in SLE, lupus, sepsis, vasculitis, inflammatory arthritis, rheumatoid arthritis and osteoarthritis, psoriasis, Alzheimer's disease, autoimmune hepatitis, juvenile idiopathic arthritis, myositis (polymyositis and dermatomyositis), Sjögren's disease, antiphospholipid antibody syndrome, Behçet's disease, spondylitis, spondyloarthritis, multiple system atrophy, Parkinson's disease, Lewy body dementia asthma, allergic rhinovirus exacerbating asthma, allergic asthma, acute respiratory distress syndrome, cystic fibrosis, fibrosis and idiopathic pulmonary fibrosis, heart failure, atherosclerosis, dry eye disease, uveitis, non-granulomatous uveitis, granulomatous uveitis, dermatitis, atopic dermatitis, COPD, bronchitis, thrombotic disease, cardiovascular disease, or diabetes, cancer, cancer metastasis, or wound healing in diabetes, cancer, cancer metastasis, and in vivo or ex vivo The present invention provides pharmaceutical compositions and methods for treating and preventing NET-related pathologies, including other NET-related pathologies such as the health of transplanted organs in vivo. NET-related pathologies include eosinophilic diseases or conditions of the skin, respiratory eosinophilic diseases or conditions, gastrointestinal eosinophilic diseases or conditions, allergic diseases or conditions, or eosinophilic diseases or conditions such as helminthic, fungal, viral or bacterial infections.

The present invention provides an antibody comprising citrulline epitope or a binding fragment thereof for use in the treatment or prevention of a disease associated with release of an extracellular trap from a cell, such as a neutrophil extracellular trap (NET)-associated disease (NET-associated disease) or an eosinophil extracellular trap (EET)-associated disease (EET-associated disease), the method comprises administering at least one dose of an antibody at a specific concentration. The present invention also provides these methods themselves. NET related diseases include systemic lupus erythematosus (SLE), lupus, septicemia, vasculitis, inflammatory arthritis, rheumatoid arthritis and osteoarthritis, psoriasis, Alzheimer's disease, autoimmune hepatitis, juvenile idiopathic arthritis, myositis (polymyositis and dermatomyositis), sicca syndrome, antiphospholipid syndrome, Behcet's disease, spondylitis, spondyloarthropathy, multi-system atrophy, and the like. Parkinson's disease, Lewy body dementia, asthma, allergic rhinovirus aggravated asthma, allergic asthma, acute respiratory distress syndrome, cystic fibrosis, fibrosis and idiopathic pulmonary fibrosis, heart failure, atherosclerosis, dry eye disease, uveitis, non-granulogenic uveitis, granulogenic uveitis, dermatitis, atopic dermatitis, COPD, bronchitis, and the like. Or other NET-related diseases, such as wound healing in diabetic patients, cancer, cancer metastasis, and transplanted organ health in vivo or in vitro. The invention also provides a pharmaceutical composition and a method for treating or preventing NET related diseases. Such as SLE, lupus, sepsis, vasculitis, inflammatory arthritis, rheumatoid arthritis and osteoarthritis, psoriasis, Alzheimer's disease, autoimmune hepatitis, juvenile idiopathic arthritis, myositis (polymyositis and dermatomyositis), sicca syndrome, antiphospholipid syndrome, Behcet's disease, spondylitis, spondyloarthropathy, multi-system atrophy, Parkinson's disease, Lewy body dementia, asthma, and the like. Allergic rhinovirus aggravated asthma, allergic asthma, acute respiratory distress syndrome, cystic fibrosis, fibrosis and idiopathic pulmonary fibrosis, heart failure, atherosclerosis, dry eye disease, uveitis, non-granulometric uveitis, granulometric uveitis, dermatitis, atopic dermatitis, COPD, bronchitis, thrombotic disease, cardiovascular disease, and the like. Or other NET-related diseases, such as wound healing in diabetic patients, cancer, cancer metastasis, and transplanted organ health in vivo or in vitro. The EET-related diseases include eosinophilic granulocyte diseases or conditions, such as eosinophilic granulocyte diseases or conditions of skin; a respiratory eosinophilic granulocyte disease or condition; gastrointestinal eosinophilic cell diseases or disorders; allergic diseases or conditions; or worm, fungus, virus or bacterial infection.

The invention discloses an application of 5-nitro-8-hydroxyquinoline in activation of a TMEM175 channel and a preparation method of the 5-nitro-8-hydroxyquinoline. The invention further discloses a method for activating the TMEM175 channel. The method comprises the step of using the 5-nitro-8-hydroxyquinoline, the pharmaceutically acceptable salt of the 5-nitro-8-hydroxyquinoline and / or the isotope derivative of the 5-nitro-8-hydroxyquinoline. According to the invention, the small molecule 5-nitro-8-hydroxyquinoline which specifically targets the TMEM175 channel and can activate the TMEM175 channel is screened, and the result proves that the 5-nitro-8-hydroxyquinoline can be used as a compound targeting the TMEM175 channel and is used for preparing medicines for treating neurodegenerative diseases, such as Parkinson's disease and / or Lewy body dementia.

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).

The novel compounds of Formula (I), and the pharmaceutically acceptable salts thereof, are NLRP3 inhibitors and may be useful in the treatment, prevention, management, improvement, control, and suppression of NLRP3-mediated diseases. The compounds of the present invention may be useful in the treatment, prevention, or management of NLRP3-mediated diseases, disorders, and conditions such as, but not limited to, obesity, gout, pseudogout, CAPS, NASH, MASH, fibrosis, osteoarthritis, atherosclerosis, heart failure, idiopathic pericarditis, myocarditis, atopic dermatitis, hidradenitis suppurativa, inflammatory bowel disease, cancer, Alzheimer's disease, Parkinson's disease, Lewy body dementia (LBD), and traumatic brain injury. (I)

Provided herein are compounds, pharmaceutical compositions, and methods of use for reducing the amount or activity of SNCA mRNA in a cell or subject, and in some instances, the amount of alpha-synuclein in a cell or subject. Such compounds, pharmaceutical compositions, and methods of use are useful for ameliorating at least one symptom or marker of synucleinopathies. Such synucleinopathies include Parkinson's disease, Lewy body dementia (DLB), diffuse Lewy body disease, Parkinson's disease dementia (PDD), pure autonomic failure, multi-system atrophy (MSA), neurological Gaucher's disease, and Alzheimer's disease.

The invention relates to combinational treatment using a monoclonal anti-alpha-synuclein antibody and an additional medicament. The antibodies can be used for treating a synucleinopathy such as Parkinson's disease (including idiopathic and inherited forms of Parkinson's disease), Diffuse Lewy Body Disease (DLBD), Lewy body variant of Alzheimer's disease (LBV), Combined Alzheimer's and Parkinson disease, pure autonomic failure and multiple system atrophy together with another medicament of the invention.

The present invention provides a method of treating neurodegenerative diseases. The method comprises the step of administering to a subject in need thereof an effective amount of a polymer-flavonoid conjugate, or a nanocomplex having an outer shell comprising one or more polymer-flavonoid conjugates and optionally an inner shell comprising one or more flavonoid oligomer and a drug such as anti-CD3 or anti-CD33 encapsulated within the shells. The present method brings therapeutic effective materials through blood-brain barrier to treat neurodegenerative diseases. The present method is effective to treat neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Lewy body dementia and Huntington's disease.

The application relates to the technical field of medicines, and particularly discloses a use of (2,4-dichlorophenyl)methylsulfenyl methane amidine and salts thereof. Specifically, the application finds that (2,4-dichlorophenyl)methylsulfenyl methane amidine and its applicable medicinal derivatives can significantly enhance memory, improve the survival rate of neuron cells of patients or promote the regeneration of neuron processes of patients, and can be used for preparing medicines and health products for treating neurological diseases (such as Alzheimer's disease, vascular dementia or Lewy body dementia).

The present disclosure provides, among other things, human codon-optimized sequences encoding presenilin 1, and methods for using the sequences in gene therapy to treat neurodegenerative diseases including, but not limited to Alzheimer's disease, frontotemporal dementia, frontotemporal lobar degeneration, Pick's disease, Lewy body dementia, memory loss, and cognitive impairment including mild cognitive impairment (MCI).

The present disclosure provides, among other things, methods for using presenilin based gene therapy to treat neurodegenerative dementia including, but not limited to Alzheimers disease, frontotemporal dementia, frontotemporal lobar degeneration, Picks disease, Lewy body dementia, memory loss, and cognitive impairment including mild cognitive impairment (MCI).

The present invention provides a method of treating a neurodegenerative disease. The method comprises the step of administering to a subject in need thereof an effective amount of a polymer-flavonoid conjugate or nanocomposite, the nanocomposites have an outer shell comprising one or more polymer-flavonoid conjugates and, optionally, an inner shell comprising one or more flavonoid oligomers, as well as drugs, such as anti-CD3 or anti-CD33, encapsulated within these shells. The methods of the invention allow therapeutically effective substances to pass through the blood-brain barrier to treat neurodegenerative diseases. The methods of the invention are effective in the treatment of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, and Huntington's disease.

The present invention discloses a method for constructing and using an animal model of dementia with Lewy bodies, and belongs to the technical field of animal model construction. The construction method comprises: obtaining a phosphatase and tensin homologous gene-induced kinase 1 gene knockout experimental animal A using gene editing technology, and crossbreeding with an Alzheimer's disease model experimental animal B simulating β-amyloid protein (Aβ) pathology, and screening offspring containing both Alzheimer's disease-related mutations and pink1 gene knockout. The model constructed by the present invention is to deposit β-amyloid protein on the basis of pink1 gene knockout, induce α-synuclein protein aggregation using β-amyloid plaques (Aβ), widely produce Lewy bodies in the cortex and hippocampus, simulate the occurrence and development process of DLB, and provide a reliable animal model for disease mechanism research and therapeutic drug screening and development.

The present invention provides a method of treating neurodegenerative diseases. The method comprises the step of administering to a subject in need thereof an effective amount of a polymer-flavonoid conjugate, or a nanocomplex having an outer shell comprising one or more polymer-flavonoid conjugates and optionally an inner shell comprising one or more flavonoid oligomer and a drug such as anti-CD3 or anti-CD33 encapsulated within the shells. The present method brings therapeutic effective materials through blood-brain barrier to treat neurodegenerative diseases. The present method is effective to treat neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Lewy body dementia and Huntington's disease.

Disclosed herein are peptides, derivatives thereof, and salts thereof, as well as pharmaceutical compositions containing them, useful alone or in combination with other therapies for treating multifactorial neurological and other diseases. The pharmaceutical compositions may include the peptides, derivatives thereof, or salts thereof, where the peptides may include at least five consecutive amino acids having the general formula: EFGHI, or derivatives thereof, and the multifactorial neurological diseases may include Lewy body variant of Alzheimer's disease (LBVAD) or vascular dementia.

This document describes a combination composition of compound 1 and fesoterodine for treating neurological disorders (e.g., schizophrenia, Alzheimer's disease psychosis, Parkinson's disease psychosis, cognitive impairment in Alzheimer's disease, psychosis in Lewy body dementia, bipolar disorder, and dyskinesia).

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.

Provided herein are artificial microRNA (miRNA) molecules for treating synucleinopathies. In some embodiments, these miRNA molecules target the expression of SNCA protein. Further provided herein are expression constructs, vectors (e.g., rAAV), cells, viral particles, and pharmaceutical compositions containing these artificial miRNA molecules. Still further provided herein are methods and kits related to the use of these miRNA molecules, e.g., for treating synucleinopathies including Parkinson’s disease, multiple system atrophy, or Lewy body dementia.

The novel compounds of Formula (I), and the pharmaceutically acceptable salts thereof, are NLRP3 inhibitors and may be useful in the treatment, prevention, management, improvement, control, and suppression of NLRP3-mediated diseases. The compounds of the present invention may be useful in the treatment, prevention, or management of NLRP3-mediated diseases, disorders, and conditions such as, but not limited to, obesity, gout, pseudogout, CAPS, NASH, MASH, fibrosis, heart failure, idiopathic pericarditis, atopic dermatitis, inflammatory bowel disease, Alzheimer's disease, Parkinson's disease, Lewy body dementia (LBD), and traumatic brain injury. (I)

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.

The present invention provides a formulation of metformin and glibenclamide for the prevention and / or treatment of neurodegenerative diseases, preferably chosen among Parkinson's disease, multiple system atrophy, amyotrophic lateral sclerosis, frontotemporal dementia, Lewy body dementia, Huntington's disease and Alzheimer's disease.

The invention discloses amine alkoxy cotinine compounds (I), pharmaceutically acceptable salts thereof, a preparation method of the amine alkoxy cotinine compounds, a pharmaceutical composition of the amine alkoxy cotinine compounds and application of the amine alkoxy cotinine compounds in preparation of drugs for treating and / or preventing nervous system diseases. Comprising but not limited to vascular dementia, Alzheimer's disease, frontotemporal dementia, Prion disease, dementia with Lewy bodies, Parkinson's disease, Huntington's disease, HIV-related dementia, multiple sclerosis, amyotrophic lateral sclerosis, neuropathic pain, cerebral arterial thrombosis, hemorrhagic stroke, nerve injury caused by cerebral trauma and other diseases;

This invention belongs to the field of microfluidic organ-on-a-chip technology, and relates to an assemblable multi-cell co-culture brain organ-on-a-chip and its applications. The multi-cell co-culture brain organ-on-a-chip consists of a lower substrate, a middle chip, and an upper chip. The upper chip has one cell culture chamber and eight inlet / outlet ports, while the middle chip has seven cell culture chambers. The six cell culture chambers are arranged in a hexagonal pattern around the central chamber, and adjacent chambers are interconnected through a micro-forestation structure. The lower substrate serves as a supporting base. Compared with existing brain organ-on-a-chips, this chip device can effectively induce and stably generate Lewy bodies, and can reproduce typical pathological features of Parkinson's disease that are difficult to achieve with traditional chips. It is particularly suitable for simulating the blood-brain barrier and co-culture systems of brain parenchymal cells, providing novel device support for the study of Parkinson's disease mechanisms and in vitro drug screening, and has significant application value in the fields of neurological disease model construction and drug development.

The present invention relates to agents, uses and methods for the treatment of synucleinopathies, in particular to novel monoclonal anti-alpha-synuclein antibodies. These antibodies can be used to treat synucleinopathies, such as Parkinson's disease, including idiopathic and genetic forms of Parkinson's disease, diffuse Lewy body disease (DLBD), Lewy body variants of Alzheimer's disease (LBV), combinatorial Alzheimer's and Parkinson's disease, pure autonomic failure, and multi-system atrophy.

The application discloses a method for constructing a Lewy body dementia mouse model and application, and the method comprises the following steps: taking the fontanel point as an origin, determining the stereotactic coordinates of the bilateral NBM of the mouse, and the coordinates are as follows: AP: -0.6 mm, ML: ±2.1 mm, DV: 4.4-4.6 mm; drilling a small hole at the skull position corresponding to the target coordinates, and stereotaxically injecting a suspension of alpha-synuclein PFFs into the bilateral NBM brain regions of the mouse, with the injection volume of each side being 1 microliter and the concentration being 2 micrograms / microliter; and after the injection is completed, the scalp incision is sutured. The application successfully constructs a DLB / PDD animal model which can cover key cognitive brain regions in pathology and stably exhibit cognitive impairment in behavior by precisely injecting PFFs into the bilateral NBM of the mouse.