43 results about "Frontotemporal Lobe Dementia" patented technology

The invention discloses a dementia identification method based on brain computer network space cross attention fusion. The dementia identification method comprises the steps that resting-state electroencephalogram signals are acquired, preprocessing and brain network construction are carried out, the frequency band power ratio is calculated, and a training set and a test set are divided; the brain network fuses the spatial information, and spatial features are obtained through an isotropic graph neural network and a local feature enhancement module; the frequency band power ratio is coded by a multi-layer perceptron to obtain frequency spectrum statistical characteristics; a bidirectional cross attention module is input, and complementary fusion features are extracted; and performing mixed pooling and splicing on the complementary fusion features, then sending the fused features to a Chebyshev Kolmogorov-Arnold network classifier, and outputting an Alzheimer's disease / frontotemporal dementia / health control (AD / FTD / HC) classification result and a cognitive scale evaluation score (MMSE). According to the method, the multi-feature complementary information is effectively integrated through joint modeling of the spatial diagram features and the global spectrum features, and the accuracy, stability and generalization ability of AD and FTD classification in a complex brain network are improved.

The invention discloses an application of serratia marcescens in preparation of a medicine for preventing or treating gradual freezing (amyotrophic lateral sclerosis, ALS) or frontotemporal dementia (FTD). Specifically, the serratia marcescens of the present invention can improve the phenotype of an asymptomatic and frontotemporal dementia model S59L by reducing mitochondrial unfolded protein response (UPRmt); meanwhile, expression of excitatory amino acid glutamic acid can be reduced, excitatory neurotoxicity can be relieved, and ALS and FTD phenotypes can be relieved through cooperation of the two.

The present invention relates to a compound of formula (I) wherein R1 is a hydrogen atom, halogen or -(C1-C2)alkyl, R2 is -halo(C1-C2)alkoxy, and R3 and R4 form together with N to which they are attached an optionally substituted 5-7 membered monocyclic heterocycloalkyl ring or an optionally substituted 8-11 membered bicyclic heterocycloalkyl ring. The present invention also relates to a medicament and a pharmaceutical composition comprising said compound of formula (I), as well as their therapeutic uses, in particular as inhibitor of NOD-like receptor protein 3 inflammasome for preventing and / or treating Parkinson's disease, frontotemporal Dementia, Multiple System Atrophy, Alzheimer's disease, Multiple Sclerosis, Amyotrophic Lateral Sclerosis or brain injury.

The invention discloses a dementia disease identification method and system based on space-time-frequency multi-dimensional feature fusion, and belongs to the technical field of smart medical treatment. The method comprises the following steps: preprocessing an electroencephalogram signal of a target user; extracting space-time-frequency multi-dimensional features of the preprocessed electroencephalogram signals; and performing classification based on the space-time-frequency multi-dimensional features to obtain a dementia disease recognition result. According to the invention, high-precision and automatic identification can be carried out on dementia diseases such as Alzheimer disease and frontotemporal dementia.

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;

The invention relates to a method for diagnosis, disease monitoring and / or therapy guidance in a patient suspected of having a neurodegenerative disease of the Frontotemporal Dementia-Amyotrophic Lateral Sclerosis-spectrum (FTD-ALS-spectrum), comprising (a.) providing a sample obtained from said patient, wherein said sample comprises extracellular vesicles, (b.) determining a level of one or more FTD-ALS-spectrum biomarkers in the extracellular vesicles of said sample, (c.) wherein the level of the one or more biomarkers is indicative of whether the patient has (and / or allows to distinguish between) a neurodegenerative disease of the FTD-ALS-spectrum comprising a Tau-proteinopathy or a neurodegenerative disease of the FTD-ALS-spectrum comprising a TAR DNA-binding protein 43 (TPD-43)-proteinopathy. The invention further relates to a kit for carrying out the method of the present invention, methods of treating patients identified using the method of the invention, methods of determining said FTD-ALS-spectrum biomarkers in the extracellular vesicles of said sample, and samples comprising extracellular vesicles and said FTD-ALS-spectrum biomarkers.

The present invention pertains to the anti-inflammatory therapeutic effect of xantohumol in spinal cord injury (SCI). The continuous administration of xanthohumol for 1-8 weeks to SCI rats resulted in improved results in 4 clinical tests used and in lowering and faster elimination of macrophages from the SCI lesion. Since the infiltration of the SCI lesion by numerous phagocytic macrophages indicates a severe destructive inflammation of extraordinary longevity, administration of xanthohumol is neuroprotective and resulted in a better and faster recovery of the locomotor function and the strength and sensory function in the hind limbs, in a shorter period of paralysis of the urinary bladder and in the recovery of the body weight lost due to the SCI surgery. Since the traumatic brain injury (TBI) involving the white matter, and stroke involving the white matter initiate the severe destructive inflammation as in the SCI, the administration of xanthohumol is expected to be anti-inflammatory and neuroprotective in both brain diseases. Since neurodegenerative diseases including Alzheimer's disease, frontotemporal dementia and Parkinson's disease, immune mediated neuroinflammation including multiple sclerosis and neuromyelitis optica and cerebrospinal infections have inflammatory pathogenesis involving microgliosis and infiltration by macrophages, the administration of xanthohumol is expected to result in therapeutic inhibition of progression of all above diseases as well as of related neurodegenerative, immune mediated and infectious diseases of the brain and of the spinal cord.

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).

A recombinant AAV (rAAV) suitable for use in treating adult onset neurodegeneration caused by granulin (GRN) haploinsufficiency, such as progranulin (PGRN)-related frontotemporal dementia (FTD), is provided. The rAAV comprises (a) an adeno-associated virus 1 capsid, and (b) a vector genome packaged in the AAV capsid, said vector genome comprising AAV inverted terminal repeats, a coding sequence for human progranulin, and regulatory sequences which direct expression of the progranulin. Also provided are a method for treating a human patient with PGRN-FTD and other adult onset neurodegeneration caused by granulin (GRN) haploinsufficiencies, comprising delivering to the central nervous system (CNS) a recombinant adeno-associated virus (rAAV) having an adeno-associated virus 1 (AAV1) capsid, said rAAV further comprising a vector genome packaged in the AAV capsid, said vector genome comprising AAV inverted terminal repeats, a coding sequence for human progranulin, and regulatory sequences which direct expression of the progranulin.

The present invention relates to compounds suitable for imaging TDP-43 (transactive response (TAR) DNA-binding protein 43 kDa) aggregates. The compounds can be used, for example, to diagnose diseases, disorders, or abnormalities associated with TDP-43 aggregates or TDP-43 proteinopathies, such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), frontotemporal dementia (FTD), and limbic-predominant late-stage TDP-43 encephalopathy (LATE).

The present invention provides a method of treating frontotemporal dementia, or a childhood genetic neurodegenerative disease such as Ataxia Telangiectasia (A-T), or neurodegenerative diseases such as Parkinson's disease or neuropsychiatric diseases comprising administering to a subject in need thereof an effective amount of chlorite composition, such as sodium chlorite. The present invention thereby provides a method of modulating the immune system in a subject in need thereof. Described herein are methods of administration and treatment.

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 invention relates to a compound of formula (I) wherein n is 1 or 2, R1 is halogen, (C1-C4) alkyl, halo (C1-C4) alkyl, (C1-C4) alkoxy, halo (C1-C4) alkoxy, ethynyl, propargyl, or (C3-C6) cycloalkyl, or two R1 form a cyclopentane ring fused to phenol; r2 and R3 represent H, cyano, ethynyl, propargyl, (C1-C4) alkyl, hydroxy (C1-C4) alkyl, or halogenated (C1-C4) alkyl, or R2 and R3 together with the atoms linking them form a (C5-C6) carbocyclic ring fused to the pyridazine ring; r4 and R5 together with the N to which they are attached form an optionally substituted 3-7 membered monocyclic heterocycloalkyl ring, 8-11 membered bicyclic heterocycloalkyl ring or 7-12 membered bicyclic heterocyclic spiro ring. The invention also relates to a medicament and a pharmaceutical composition comprising said compounds of formula (I) and to their therapeutic use, in particular as inhibitors of NOD-like receptor protein 3 inflammasome for the treatment of e.g. Parkinson's disease or frontotemporal dementia.

An EEG-based dementia diagnosis assistance device according to the present embodiment comprises: an EEG data preprocessing unit for preprocessing a collected EEG data set of a test subject, the collected EEG data set being divided into time intervals by setting a window length and a shift length; an Hjorth parameter extraction unit for extracting, for each time interval, Hjorth parameters including an activity index, a mobility index, and a complexity index; and a dementia classification unit for classifying the test subject into one from among a Alzheimer's disease (AD) group, a frontotemporal dementia (FTD) group, and a cognitive normal (CN) group on the basis of the extracted Hjorth parameters. Therefore, AD, FTD, and CN subjects can be classified using Hjorth parameters composed of three major indicators of activity, mobility, and complexity through time domain analysis on EEG datasets.

Aspects of the disclosure relate to methods and compositions (e.g., kits) for detecting anti-repeat-associated non-ATG (RAN) protein antibodies in a subject (e.g., a subject that has been administered a therapeutic anti-RAN protein antibody or a vaccine against a disease or disorder associated with RAN protein expression, translation, and / or accumulation, for example amyotrophic lateral sclerosis (ALS) and / or frontotemporal dementia (FTD)). In some embodiments, methods described by the disclosure comprise detecting one or more anti-RAN protein antibodies in a biological sample obtained from a subject by an electrochemiluminescence-based immunoassay using one or more target di-amino acid repeat peptides. In some embodiments, the disclosure relates to kits comprising one or more di-amino acid repeat peptides and an electrochemiluminescence-based immunoassay plate and / or reagents.

Among other things, the present disclosure provides oligonucleotide compositions and methods thereof. In some embodiments, oligonucleotides comprise various chemical modifications of sugars, nucleobases, and / or internucleotidic linkages and patterns thereof and are usefill for exon skipping. In some embodiments, the present disclosure provides technologies useful for skipping cryptic exons of stathmin-2(STMN2) transcripts. In some embodiments, the present disclosure provides technologies useful for modulating STMN2 transcript splicing. In some embodiments, the present disclosure provides methods for preventing or treating conditions, disorders or diseases including neurodegenerative diseases, e.g,, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

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.

Disclosed herein are compositions and methods for reducing expression of C9ORF72 mRNA and protein in an animal with C9ORF72 specific inhibitors. Such methods are useful to treat, prevent, or ameliorate neurodegenerative diseases in an individual in need thereof. Such C9ORF72 specific inhibitors include antisense compounds. Examples of neurodegenerative diseases that can be treated, prevented, and ameliorated with the administration C9ORF72 specific inhibitors include amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), corticalbasal degeneration syndrome (CBD), atypical Parkinsonian syndrome, and olivopontocerellar degeneration (OPCD).

The present disclosure provides the use of compounds of Formulae (I), (II), (III), (III-A), and (III-B) (e.g., metformin) in treating a neurological disease associated with repeat expansions and / or RAN protein accumulation, reducing the level of one or more repeat associated non-ATG (RAN) proteins, and reducing the accumulation of RAN proteins in a subject and / or biological sample. Also provided is the use of compounds of Formulae (I), (II), (III), (III-A), and (III-B) (e.g., metformin) in inhibiting RAN protein translation in a subject and in a biological sample (e.g., cells, tissue). Also provided in the present disclosure are pharmaceutical compositions, kits, and uses of compounds of Formulae (I), (II), (III), (III-A), and (III-B) (e.g., metformin) for treating diseases associated with repeat expansions. Exemplary diseases associated with repeat expansions include, but are not limited to, C9ORFf72 amyotrophic lateral sclerosis (ALS), or C9ORFf72 frontotemporal dementia; myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2); spinocerebellar ataxia; Huntington's disease; Fragile X Tremor Ataxia Syndrome (FXTAS); and Fragile XE syndrome (FRAXE).

The invention discloses 2-sulfur-3-(piperidinedithio) phthalide (I), pharmaceutically acceptable salts thereof, a preparation method of the 2-sulfur-3-(piperidinedithio) phthalide (I), a pharmaceutical composition of the 2-sulfur-3-(piperidinedithio) phthalide (I) and application of the 2-sulfur-3-(piperidinedithio) phthalide (I) in preparation of drugs for treating and 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;

The disclosure describes improved vectors, such as adeno-associated virus (AAV) vectors, for expressing progranulin and variants thereof in transduced cells, and use of such vectors to increase the amount of progranulin in subjects experiencing a progranulin deficiency, such as certain subjects with frontotemporal dementia (FTD) or frontotemporal lobar degeneration (FTLD).

The application discloses an Alzheimer and frontotemporal dementia diagnosis device based on electroencephalogram, wherein the device comprises: collecting electroencephalogram data of a patient to be diagnosed; converting the electroencephalogram data into CSD images and PSD images by using an MNE library; expanding the CSD images and the PSD images by adopting a bilinear interpolation method to obtain CSD and PSD images with consistent width and height; merging the expanded CSD images and the PSD images to form a three-dimensional tensor with eight channels; inputting the three-dimensional tensor into a diagnosis model, and performing prediction based on the diagnosis model to obtain a prediction result; and classifying and comparing the prediction result with diagnosis standards of Alzheimer and frontotemporal dementia to obtain the prediction result and diagnose the patient. The method can efficiently and accurately analyze and diagnose electroencephalogram signals by optimizing the structure and parameters of the model, so that more accurate, rapid and objective disease diagnosis is realized.

The invention relates to an auxiliary diagnosis system and device for neurodegenerative diseases and a storage medium. Based on a single molecule immunoassay technology, the relevance between the ratio of a P-tau217 concentration value and an A beta 42 concentration value and the neurodegenerative disease is deeply analyzed, a reference interval is designed, and an efficient screening tool is further developed; and high-specificity, high-sensitivity and high-accuracy auxiliary screening of neurodegenerative diseases such as Alzheimer's disease, subcortical ischemic vascular dementia and frontotemporal dementia is realized.

The present invention provides oligonucleotides, compositions, and methods for preventing and / or treating various pathological conditions, disorders, or diseases. [Solution] In some embodiments, the provided technology comprises nucleic acid base modification, sugar modification, internucleotide linkage modification and / or patterns thereof, and has improved properties, activity and / or selectivity. In some embodiments, the provided technology targets MAPT. In some embodiments, the disclosure provides MAPT oligonucleotides, compositions and methods for preventing and / or treating MAPT-related conditions, disorders or diseases, such as Alzheimer's disease (AD) or frontotemporal dementia (FTD).

This invention discloses a dementia identification method based on spatial cross-attention fusion using brain-computer networks, comprising: acquiring resting-state electroencephalogram (EEG) signals, performing preprocessing and brain network construction, calculating frequency band power ratios, and dividing the dataset into training and testing sets; fusing spatial information through the brain network, and obtaining spatial features via an isovariant graph neural network and a local feature enhancement module. The frequency band power ratio is encoded by a multilayer perceptron to obtain spectral statistical characteristics. ;Will and Input a bidirectional cross-attention module to extract complementary fusion features; The complementary fusion features are mixed and pooled, then concatenated and fed into a Chebyshev Kolmogorov–Arnold network classifier to output classification results for Alzheimer's disease / frontotemporal dementia / healthy controls (AD / FTD / HC) and cognitive scale evaluation scores (MMSE). This invention effectively integrates complementary information from multiple features by jointly modeling spatial graph features and global spectral features, thereby improving the accuracy, stability, and generalization ability of AD and FTD classification in complex brain networks.

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;

The invention discloses a 3-(piperidine alkyl dithioalkyl) phthalide compound (I), pharmaceutically acceptable salts thereof, a preparation method thereof, a pharmaceutical composition thereof and application of the 3-(piperidine alkyl dithioalkyl) phthalide 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;

The present invention relates to a therapeutic composition for treating, preventing, inhibiting, and improving or slowing down the onset or progression of degenerative nervous system diseases, particularly diseases associated with the aggregate formation of TAR DNA-binding protein 43 (TDP-43), such as amyotrophic lateral sclerosis, using a combination agent containing colchicine or a pharmaceutically acceptable salt thereof and metformin or a pharmaceutically acceptable salt thereof as active ingredients. Examples of diseases associated with TDP-43 protein include frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), chronic traumatic encelopathy (CTE), and limbic-predominant age-related TDP-43 encephalopathy (LATE). and diseases, disorders and abnormalities associated with TDP-43, particularly those associated with TDP-43 aggregates, or TDP-43 proteinopathies. The inventors of the present invention have confirmed that the above-mentioned degenerative diseases can be treated or prevented by using a combination of colchicine and metformin, which are drugs not used in the prior art, as a therapeutic agent for the diseases.

The present disclosure encompasses engineered meganucleases that bind and cleave recognition sequences within a C9Orf72 gene. The present disclosure also encompasses methods of using such engineered meganucleases to make genetically modified cells. Further, the disclosure encompasses pharmaceutical compositions comprising engineered meganuclease proteins, or polynucleotides encoding engineered meganucleases of the disclosure, and the use of such compositions for the modification of a C9Orf72 gene in a subject, or for treatment of amyotrophic lateral sclerosis (ALS) and / or frontotemporal dementia (FTD).

This invention discloses a class of 3-substituted phthalide compounds (I) and their pharmaceutically acceptable salts, their preparation methods, pharmaceutical compositions, and their use in the preparation of drugs for the treatment and / or prevention of neurological diseases, including but not limited to vascular dementia, Alzheimer's disease, frontotemporal dementia, Prion's disease, Lewy body dementia, Parkinson's disease, Huntington's disease, HIV-related dementia, multiple sclerosis, amyotrophic lateral sclerosis, neuropathic pain, ischemic stroke, hemorrhagic stroke, and neurological damage caused by traumatic brain injury;