463 results about "Amyotrophic lateral sclerosis" patented technology

The present disclosure provides methods, uses, kits, and compositions comprising a compound of Formula (I), and either a second compound of Formula (I) or a compound of Formula (II). In one aspect, the methods are for treating a neurological disease associated with repeat expansions and / or RAN protein accumulation, reducing the level of one or more repeat associated non-AUG (RAN) proteins, and reducing the accumulation of RAN proteins in a subject and / or biological sample. Exemplary diseases associated with repeat expansions include, but are not limited to, amyotrophic lateral sclerosis (ALS), frontotemporal dementia, myotonic dystrophy type 1, myotonic dystrophy type 2, spinocerebellar ataxia, Alzheimer's disease, Huntington's disease, Fragile X Tremor Ataxia Syndrome, and Fragile XE syndrome.

Aspects of the disclosure relate to compositions and methods for the diagnosis and / or treatment of C9orf72 negative sporadic amyotrophic lateral sclerosis (C9− sALS). In some embodiments, the disclosure relates to identifying a subject as having C9orf72 negative (C9−) sALS by detecting expression or activity of repeat-associated non-ATG (RAN) translation proteins (e.g., RAN proteins). In some embodiments, the methods and compositions of the disclosure identify certain gene or genes which comprise mutation(s) leading to the expression of the detected RAN proteins, and which were previously unknown to be associated with sALS. In some embodiments, said gene(s) can be used to identify or diagnose subjects having, suspected of having, or at risk of developing sALS which is unrelated to expansion mutations within the C9orf72 and / or SCA36 genetic loci (e.g., C9− sALS). In some embodiments, the disclosure relates to methods of treating C9− sALS by administering to a subject in need thereof an agent that reduces expression or activity of RAN proteins.

Disclosed herein are methods and compositions for identifying and / or treating subjects having or likely to have amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD). Antibodies specific for one or more di-amino acid repeat-containing proteins are also provided herein.

The invention features polypeptides that include an extracellular ActRIIa variant. In some embodiments, a polypeptide of the invention includes an extracellular ActRIIa variant fused to an Fc domain monomer or moiety. The invention also features pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions involving weakness and atrophy of muscles, e.g., Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, inclusion body myositis, amyotrophic lateral sclerosis, sarcopenia; or cancer cachexia; or metabolic diseases, e.g., obesity, Type-1 diabetes, or Type-2 diabetes.

The present invention relates to a method of treating a glucose-6-phosphate dehydrogenase dysregulated disorder in a subject in need thereof, the method comprising administering to the subject an effective amount of oleanolic acid, a conjugated salt thereof, or a prodrug thereof. The glucose 6-phosphate dehydrogenase dysregulated disorder can be myofibrillar myopathy, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease and Alzheimer's disease caused by BCL2 associated immortal gene mutation.

The present disclosure relates generally to compositions and methods for inhibiting dipeptide repeat protein (DPR)-ribosomal RNA (rRNA) interaction. In particular, the present technology relates to administering a therapeutically effective amount of one or more compositions that inhibit DPR-rRNA interaction to a subject diagnosed with, or at risk for DPR-associated pathologies, e.g., amyotrophic lateral sclerosis or frontotemporal dementia.

Methods, systems, and techniques for controlling actuators by using eye gaze technology such as in a wheelchair or bed, are provided. Example embodiments provide an Eye Gaze Actuator Control System (“EGACS”) which enables people with advanced motor neuron diseases or disabilities like amyotrophic lateral sclerosis or muscular dystrophy to use eye gaze technologies to control their actuators that control seating, bed positioning, and movement of motor-controlled devices. In one embodiment, the example EGACS comprises a display device, eye gaze sensor, eye gaze control application, and device interface(s) to one or more other devices that control aspects of a powered wheelchair, bed, vehicle, or other device. These components cooperate to control the powered wheelchair, bed, or vehicle using eye gaze technology as opposed to by manual control.

The BAG3 proteins are useful in the treatment of Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, Lewy body disease, vascular dementia, mixed dementia and traumatic brain injury, such as chronic traumatic encephalopathy (CTE). A therapeutic BAG3 composition, use of BAG3, and a method of treatment of BAG3 are described.

Disclosed herein are UNC13A oligonucleotides with one or more spacers or without a spacer. In various embodiments, UNC13A oligonucleotides with spacer(s) reduce mis-spliced UNC13A transcripts and increase full length UNC13A transcripts, thereby imparting therapeutic efficacy against neurological diseases such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), or Alzheimer's disease (AD).

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 humanized TDP-43 specific binding molecules, in particular to humanized anti-TDP-43 antibodies or antigen-binding fragment or a derivative thereof 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).

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.

Disclosed herein are methods of treating ALS in a subject by administering a therapeutically effective amount of a composition comprising EVs, e.g., derived from neural cells, e.g., neural progenitor cells, to the subject. The EVs can be administered distally or peripherally to the CNS, such that the EVs cross the blood brain barrier and exert their therapeutic function in the CNS. The methods can reduce inflammation (e.g., NLRP3 inflammatory pathway signaling), reduce disease activity or progression, and / or improve motor or neurological performance, signs or symptoms associated with ALS, or survival in the ALS subject as compared to a control ALS subject. The methods of inhibiting necroptosis in a cell by contacting the cell with a therapeutically effective amount of a composition comprising EVs are also provided.

Provided herein are optionally substituted pyrazolylacetamides, pharmaceutical compositions comprising a therapeutically effective amount of such compounds and a pharmaceutically acceptable excipient, and methods of treating diseases or disorders, such as, epilepsy, amyotrophic lateral sclerosis, various types of pain, hyperexcitability, a dyskinesia, dystonia, mania, tinnitus, neurodevelopmental diseases or disorders, a smooth muscle contractility disorder, Dravet syndrome, posttraumatic stress disorder (PTSD), with such compounds and pharmaceutical compositions.

The invention features polypeptides that include an extracellular ActRIIa variant. In some embodiments, a polypeptide of the invention includes an extracellular ActRIIa variant fused to an Fc domain monomer or moiety. The invention also features pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions involving weakness and atrophy of muscles, e.g., Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, inclusion body myositis, amyotrophic lateral sclerosis, sarcopenia; or cancer cachexia; or metabolic diseases, e.g., obesity, Type-1 diabetes, or Type-2 diabetes.

The invention belongs to the technical field of medicines, and discloses application of hyperforin in preparation of a medicine for preventing or treating amyotrophic lateral sclerosis. The hyperforin can improve the survival rate of stable transfection cell lines of amyotrophic lateral sclerosis related cell models (SOD1G93A / TDP43M337V), and the hyperforin is prompted to play a protective role in the two cell models. After the hyperforin is given, the expression levels of HO-1 and Drp1 proteins in SOD1G93A cells are increased, which indicates that the hyperforin has certain antioxidant activity; and mitochondrial division in cells can be inhibited, so that cell apoptosis is inhibited and retarded, and a protection effect is achieved. Hypericin can help to improve the SOD1G93A cell morphology and promote synaptic generation, and it is prompted that hypericin has a positive effect on maintaining normal functions of cells. In conclusion, the hyperforin plays a protective role in an SOD1G93A cell model and a TDP43M337V cell model, and the mechanism of the hyperforin is possibly related to the antioxidant activity, the mitochondrial function improvement and the like of the hyperforin.

The present invention includes compositions and methods of treating CNS-related conditions, comprising: administering an effective amount of a compound that lowers the levels of one or more branched-chain amino acids (BCAAs) or metabolites thereof, or any pharmaceutically acceptable salt thereof, wherein the CNS-related conditions is selected from the group consisting of Alzheimer's disease and any related forms of dementia including vascular dementia, Lewy body dementia, frontotemporal dementia, Creutzfeldt-Jacob disease, Wernicke-Korsakoff disease, and Huntington's disease, Multiple sclerosis, Parkinson's disease, autism, Amyotrophic lateral sclerosis (ALS), Hereditary diffuse leukoencephalopathy with spheroids (HDLS) and epilepsy.

The invention provides application of adiponectin and an adiponectin receptor agonist in treatment of amyotrophic lateral sclerosis. The invention finds that the plasma adiponectin level of an ALS patient is related to the inflammatory factor level, and finds that AdipoR1 and AdipoR2 in the ALS patient are remarkably up-regulated and are related to M1 type macrophage activation. Experiments prove that the adiponectin receptor stimulant can relieve the proinflammatory response of macrophages, regulate the polarization of the macrophages and protect neurons, and the adiponectin receptor stimulant can postpone the occurrence of dyskinesia of ALS patients and prolong the lifetime of the ALS patients. The invention provides a new strategy for diagnosis and treatment of ALS, and has a good clinical application prospect.

To provide 2-aminopyridine derivative compounds for use as inhibitors of nitric oxide synthase.SOLUTION: Disclosed are 2-aminopyridine derivative compounds for use as inhibitors of nitric oxide synthase (NOS). In particular, the field of the present invention relates to 2-aminopyridine derivative compounds for use as inhibitors of neuronal nitric oxide synthase (nNOS), which are formulated as pharmaceutical compositions for treating nNOS-associated diseases and disorders such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, as well as amyotrophic lateral sclerosis, cerebral palsy, stroke / ischemic brain injury, and migraine headaches.SELECTED DRAWING: Figure 1

Provided herein are methods for decreasing Ataxin-2 mRNA expression. Such methods are useful to ameliorate symptoms of Ataxin-2 associated diseases. Such Ataxin-2 associated diseases include amyotrophic lateral sclerosis (ALS). Such symptoms include loss of motor function, reduced CMAP amplitude, denervation, and loss of motor neurons.

Provided herein are optionally substituted pyrazolylacetamides, pharmaceutical compositions comprising a therapeutically effective amount of such compounds and a pharmaceutically acceptable excipient, and methods of treating diseases or disorders, such as, epilepsy, amyotrophic lateral sclerosis, various types of pain, hyperexcitability, a dyskinesia, dystonia, mania, tinnitus, neurodevelopmental diseases or disorders, a smooth muscle contractility disorder, Dravet syndrome, posttraumatic stress disorder (PTSD), with such compounds and pharmaceutical compositions.

The present invention relates to an improved antibody specifically binding to amyloid-β oligomers (AβOs). Specifically, the present invention relates to an improved form of the antibody W20. Compared with the antibody W20, the improved form of the antibody W20 has a significantly improved affinity to AβOs, and can more significantly inhibit the aggregation of Aβ and the AβOs-induced toxicity of nerve cells, more effectively improve the cognition and memory functions of an Alzheimer's disease model mouse, and reduce pathological changes in the brain of the mouse. The improved form of the antibody can specifically bind to oligomers of an amyloid-β, α-synuclein, mHTT and SOD 1, can inhibit the aggregation and cytotoxicity of various amyloids, and has a better potential for treating various amyloid diseases, such as Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, than the antibody W20. The improved form of the antibody can specifically bind to a highly toxic amyloid protein oligomer Aβo*3F, and has a better AD diagnosis value. The amino acid sequence of the antibody W20 is as shown in SEQ ID NO: 1.

Aspects of the disclosure relate to recombinant gene editing complexes comprising a recombinant gene editing protein and guide RNA (gRNA) that specifically hybridizes to a region of a C90RF72 gene (e.g., a region flanking a G4C2 repeat or within a exonic region of the gene).

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 application relates to an NEK7 inhibitor, a pharmaceutical composition and a use thereof. The compound has a structural formula of formula (I). The compound of the present disclosure has good NEK7 inhibitory activity, and can be used for treating or preventing inflammatory pathological disorders (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, atopic dermatitis, ulcerative colitis, Crohn's disease, cancer, osteoarthritis, gout, etc.) regulated by the NLRP3 inflammasome.

Provided herein are optionally substituted pyrazolylacetamides, pharmaceutical compositions comprising a therapeutically effective amount of such compounds and a pharmaceutically acceptable excipient, and methods of treating diseases or disorders, such as, epilepsy, amyotrophic lateral sclerosis, various types of pain, hyperexcitability, a dyskinesia, dystonia, mania, tinnitus, neurodevelopmental diseases or disorders, a smooth muscle contractility disorder, Dravet syndrome, posttraumatic stress disorder (PTSD), with such compounds and pharmaceutical compositions.

The present invention relates to activin receptor IIA type variants and methods of use thereof. The present invention features a polypeptide comprising an extracellular ActRIIa variant. In some embodiments, the polypeptides of the present invention comprise an extracellular ActRIIa variant fused to an Fc domain monomer or part. The invention also features the treatment of diseases and conditions involving muscle weakness and atrophy using said polypeptides, such as Duchenne muscular dystrophy, facial shoulder brachial muscular dystrophy, inclusion body myositis, amyotrophic lateral sclerosis, sarcopenia; or cancer cachexia; the present invention relates to pharmaceutical compositions and methods for treating a metabolic disease, such as obesity, type 1 diabetes mellitus or type 2 diabetes mellitus.

Aspects of the disclosure relate to compositions and methods for the diagnosis and / or treatment of certain neurodegenerative diseases, for example those diseases associated with repeat-associated non-ATG (RAN) translation proteins, such as amyotrophic lateral sclerosis (ALS). In some embodiments, the disclosure relates to recombinant adeno-associated viruses (rAAVs) expressing antibodies and antigen-binding fragments thereof that bind to poly(GA) RAN proteins. In some embodiments, the disclosure relates to methods of treating a RAN protein-associated disease by administering to a subject in need thereof the rAAVs.

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.

A personalized medical method for treating amyotrophic lateral sclerosis (ALS), comprising screening out a subpopulation of ALS patients having highly immunologically active causes, and administering a therapeutically effective amount of a Janus kinase (JAK) inhibitor to the patients screened out thereby. Also provided are the use of a corresponding JAK inhibitor, an in vitro diagnostic method for screening patients, a kit, and a computer-implemented method. After patients screened out by means of the method are treated with a JAK inhibitor (such as tofacitinib), the level of a nerve damage marker is significantly reduced, and clinical functions are stabilized or improved, and therefore the present invention shows a good therapeutic prospect.

The present invention discloses the use of fosfomycin as the sole active ingredient in the preparation of a drug for preventing and / or treating amyotrophic lateral sclerosis (ALS). The chemical formula of fosfomycin is C3H7O4P. The drug is used to prevent and / or treat ALS characterized by an abnormal number of GGGGCC sequence repeats in the C9orf72 gene. Using an ALS fruit fly model and phenotypic experiments, the present invention demonstrates that fosfomycin is non-toxic to Drosophila and can attenuate the neurodegenerative phenotype of ALS fruit flies. The application of fosfomycin in the treatment of ALS, particularly ALS characterized by an abnormal number of GGGGCC sequence repeats in the C9orf72 gene, has practical value.