52 results about "Epileptic encephalopathy" patented technology

Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of SCN2A RNA in a cell or subject, and in certain instances reducing the amount of SCN2A protein in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a disease or disorder associated with a voltage-gated sodium channel protein, such as, for example, a Developmental and Epileptic Encephalopathy, an intellectual disability, or an autism spectrum disorder. Such symptoms and hallmarks include, but are not limited to seizures, hypotonia, sensory integration disorders, motor development delays and dysfunctions, intellectual and cognitive dysfunctions, movement and balance dysfunctions, visual dysfunctions, delayed language and speech, gastrointestinal disorders, neurodevelopmental delays, sleep problems, and sudden unexpected death in epilepsy.

Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of SCN2A RNA in a cell or subject, and in certain instances reducing the amount of SCN2A protein in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a disease or disorder associated with a voltage-gated sodium channel protein, such as, for example, a Developmental and Epileptic Encephalopathy, an intellectual disability, or an autism spectrum disorder. Such symptoms and hallmarks include, but are not limited to seizures, hypotonia, sensory integration disorders, motor development delays and dysfunctions, intellectual and cognitive dysfunctions, movement and balance dysfunctions, visual dysfunctions, delayed language and speech, gastrointestinal disorders, neurodevelopmental delays, sleep problems, and sudden unexpected death in epilepsy.

The human gene SCN2A encodes human SCN2A protein, the alpha-1 subunit of the voltage-gated sodium channel Nav 1.2. Mutations in SCN2A are associated with a variety of neurodevelopmental and intellectual diseases and disorders, including developmental and epileptic encephalopathy (DEE), such as early-onset DEE. Compositions and methods of using SCN2A oligomeric compounds for treating SCN2A related disorders, including early onset developmental and epileptic encephalopathy.

The invention discloses a pharmaceutical composition for treating KCNQ2 developmental epileptic encephalopathy, a nucleic acid construct and application of the pharmaceutical composition and the nucleic acid construct. According to the invention, by introducing a nucleic acid construct carrying the hKCNQ2 gene into a KCNQ2A294V / + developmental epileptic encephalopathy animal model and a human forebrain neuron model, the effectiveness of the nucleic acid construct in improving the expression level of the KCNQ2 and improving related neuropathological mechanisms is verified. Not only is a new hope provided for treatment of KCNQ2-related developmental epileptic encephalopathy provided, but also a new direction is opened up for application of gene therapy in neurodevelopmental diseases.

Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof, wherein Ring A, Ring B, R1, R2, R3, R12, and L are as defined herein. The compounds are antagonists of the resistant (R-type) voltage-gated calcium ion channel Cav 2.3. Also disclosed are pharmaceutical compositions comprising the compounds; and the compounds for use in the treatment of diseases modulated Cav 2.3, including epilepsy, neurodegenerative conditions such as Parkinson's disease, focal, drug-resistant forms of epilepsy, and other neurological disorders such as developmental and epileptic encephalopathies and Phelan-McDermid and Fragile X syndromes.

Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof wherein Ring A, Ring B, R1, R2, R3 and L are as defined herein. The compounds are antagonists of the resistant (R-type) voltage-gated calcium ion channel Cav 2.3. Also disclosed are pharmaceutical compositions comprising the compounds; and the compounds for use in the treatment of diseases modulated Cav 2.3, including epilepsy, neurodegenerative conditions such as Parkinson's disease, focal, drug-resistant forms of epilepsy, and other neurological disorders such as developmental and epileptic encephalopathies and Fragile X syndrome.

Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof, wherein Ring A, Ring B, R1, R2, R3, R12, and L are as defined herein. The compounds are antagonists of the resistant (R-type) voltage-gated calcium ion channel Cav 2.3. Also disclosed are pharmaceutical compositions comprising the compounds; and the compounds for use in the treatment of diseases modulated Cav 2.3, including epilepsy, neurodegenerative conditions such as Parkinson's disease, focal, drug-resistant forms of epilepsy, and other neurological disorders such as developmental and epileptic encephalopathies and Phelan-McDermid and Fragile X syndromes.

The disclosure relates to polynucleotides, e.g., viral genomes, encoding syntaxin-binding protein-1 (STXBP1), vectors, e.g., adeno-associated virus (AAV) particles, comprising said polynucleotides, compositions comprising said polynucleotides or vectors, and methods of making or delivering to a cell or subject. The polynucleotides, vectors, compositions, and methods of the present disclosure are useful for the treatment of subjects who have, have been diagnosed with having, or are at risk of having a STXBP1-related disorder, e.g., STXBP1 Developmental and Epileptic Encephalopathy (DEE) and / or other STXBP1-related disorders, or at least one symptom thereof.

Provided herein are compounds and pharmaceutical compositions comprising a therapeutically effective amount of such compounds, or pharmaceutically acceptable salts, and a pharmaceutically acceptable excipient, and methods of treating neurodevelopmental diseases or disorders (NDD) and developmental and epileptic encephalopathy (DEE), comprising administering such compounds, or pharmaceutically acceptable salts, and pharmaceutical compositions, to pediatric patients.

The disclosure relates to adeno-associated (AAV) particles comprising viral genomes encoding cyclin-dependent kinase-like 5 (CDKL5) proteins and peptides, compositions comprising said AAV particles, and methods for making and delivering said AAV particles to a cell or subject. The AAV particles, compositions, and methods of the present disclosure are useful for the treatment of subjects who have, have been diagnosed with having, or are at risk of having a CDKL5 deficiency disorder (CDD), developmental and epileptic encephalopathy 2, atypical Rett syndrome, and / or other CDKL5-related disorders or at least one symptom thereof.

Provided are methods of treating a subject with a SCN2A-related disorder, e.g., Developmental and Epileptic Encephalopathies (DEE), comprising administering to the subject an oligomeric compound. Also provided are methods of reducing frequency of seizures experienced by a subject with a SCN2A-related disorder, comprising administering to the subject an oligomeric compound.

The invention discloses a preparation method of a composition containing uridine and application thereof in treating developmental epileptic encephalopathy type 50, belonging to the technical field of pharmaceutical compositions. The preparation method comprises the following steps: preparing a disintegrant, preparing a uridine complex, preparing a tablet core, preparing a coating liquid, and coating; the preparation of the disintegrant comprises the following steps: preparing an aqueous phase, preparing an oil phase, cross-linking, primary modification, and secondary modification; the preparation of the uridine complex comprises the following steps: surface treatment and loading; the preparation of the tablet core comprises uniformly mixing the uridine complex, the disintegrant, hydroxypropyl methylcellulose, and magnesium stearate, and then tabletting to obtain the tablet core; the uridine-containing composition prepared by the invention has small weight difference and high hardness, is not easy to peel off the coating during preparation, storage, and transportation, is not easy to break and deform during preparation and transportation, and has a fast disintegration speed.

The present technology relates to methods of treating behavioral problems and seizures in a subject having developmental and epileptic encephalopathy (DEE) by transdermally administering an effective amount of cannabidiol (CBD) to the subject wherein behavioral problems are treated in the subject.

The present disclosure relates generally to methods for determining whether a patient suffering from or at risk for STXBP1- or SYNGAP1-encephalopathy will benefit from treatment with phenylbutyrate compositions comprising screening the patient for mutations in STXBP1 or SYNGAP1. Also disclosed herein are methods for selecting patients at risk for developmental and epileptic encephalopathy (DEE) for treatment with compositions including phenylbutyrate.

Compositions and methods of use of SCN2A oligomeric compounds for treating SCN2A-associated disorders, including early onset developmental and epileptic encephalopathies. In certain embodiments, the SCN2A-associated disorder is early onset developmental or epileptic encephalopathies (DEEs). In certain embodiments, the SCN2A-associated disorder is DEEs, including, for example, Ohtahara syndrome; epilepsy with migrating focal seizures of infancy (EIMFS); infantile and pediatric DEEs, such as West syndrome and Lennox-Gastaut syndrome; Dravet syndrome; idiopathic / generalized epilepsy (IGE / GGE); temporal lobe epilepsy; myoclonic atonic epilepsy (MAE); migratory partial epilepsy of infancy (MMPSI); and familial hemiplegic migraine with or without epilepsy.

Aspects of the present invention relate to a method of treating an epileptic encephalopathy in a mammal in need thereof, comprising administering a composition comprising an effective amount of (1-benzyl-1-hydroxypiperidin-1-yl) (2,4′-bipyridin-3-yl)methanone or a pharmaceutically acceptable salt thereof to the mammal.

This invention provides a treatment for patients with developmental and epileptic encephalopathy (DEE) that addresses behavioral problems in addition to seizures, without causing undesirable side effects such as somnolence, lethargy, withdrawal, and sedation. [Solution] A method is provided for treating behavioral problems and seizures in a subject having DEE, comprising administering an effective amount of cannabidiol (CBD) transdermally to the subject, wherein the behavioral problems are treated in the subject.

Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of SCN2A RNA in a cell or subject, and in certain instances reducing the amount of SCN2A protein in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a disease or disorder associated with a voltage-gated sodium channel protein, such as, for example, a Developmental and Epileptic Encephalopathy, an intellectual disability, or an autism spectrum disorder. Such symptoms and hallmarks include, but are not limited to seizures, hypotonia, sensory integration disorders, motor development delays and dysfunctions, intellectual and cognitive dysfunctions, movement and balance dysfunctions, visual dysfunctions, delayed language and speech, gastrointestinal disorders, neurodevelopmental delays, sleep problems, and sudden unexpected death in epilepsy.

Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof: (I) wherein Ring A, R1, R2, R3, R4, Y1, Y2, Y3, Y4, a, t, u, and L are as defined herein. The compounds are antagonists of the resistant (R-type) voltage-gated calcium ion channel Cav 2.3. Also disclosed are pharmaceutical compositions comprising the compounds; and the compounds for use in the treatment of diseases modulated Cav 2.3, including neurodegenerative conditions such as Parkinson's disease, focal, drug-resistant forms of epilepsy, and other neurological disorders such as developmental and epileptic encephalopathies and Fragile X syndrome.

Provided are methods of treating a subject having an SCN2A-related disorder, such as developmental and epileptic encephalopathy (DEE), comprising administering to the subject an oligomeric compound. Also provided are methods of reducing the frequency of epileptic seizures experienced by a subject suffering from an SCN2A-related condition, the method comprising administering to the subject an oligomeric compound.

The present invention belongs to the technical field of auxiliary diagnosis of epileptic encephalopathy, and specifically relates to an automatic quantification and prognosis assessment model for ESES-related epileptic encephalopathy and its training and usage methods. The encephalopathy automatic quantification and prognosis assessment model of the present invention includes a brain network feature extraction module, an electroencephalogram (EEG) depth feature extraction module, and an identification and diagnosis module; the brain network feature extraction module includes a calculation module, a graph convolutional neural network, and an attention mechanism network, which obtain brain network graph theory features and atlas features, and fuse the two to obtain information on the state transition between data segments; the EEG depth feature extraction module is used to extract EEG depth features; the identification and diagnosis module is used to fuse the brain network features extracted by the EEG depth feature extraction module and the EEG depth features extracted by the EEG depth feature extraction module, and perform the identification of ESES characteristic waves and the assessment of the prognosis level. The present invention not only realizes the automatic quantification of ESES, but also realizes the prognosis assessment of ESES-related epileptic encephalopathy, thereby greatly improving the diagnosis and treatment efficiency of ESES.

RNA interference-based methods and products for inhibiting the expression of pathogenic dynamin-1 variants are provided. Delivery vehicles such as recombinant adeno-associated viruses deliver DNAs encoding RNAs that inhibit the expression of the dynamin-1 variants. The methods treat, for example, developmental and epileptic encephalopathies.

Disclosed herein are products, methods, and uses for treating, ameliorating, or delaying the progression of, and / or preventing seizures, an epileptic disease or disorder, an intellectual or developmental disability, autism, or an autism spectrum disorder associated with mutant or pathogenic Potassium Channel, Voltage Gated KQT-Like Subfamily Q, Member 3 (KCNQ3) expression. More particularly, disclosed herein are RNA interference-based products, methods, and uses for reducing or inhibiting the expression of the KCNQ3 gene and its resulting mRNA and / or protein. Even more particularly, the disclosure provides microRNA (miRNA) for reducing or inhibiting the expression of KCNQ3 and methods of using said miRNA to reduce or inhibit mutant or pathogenic KCNQ3 expression in cells and / or in cells of a subject having a genetic mutation in the KCNQ3 gene which results in disease symptoms including, but not limited to, seizures, epilepsy, intellectual and / or developmental disability, autism, or an autism spectrum disorder. Such disease symptoms, in some aspects, result from developmental and epileptic encephalopathy (DEE) attributed to various mutations in the KCNQ3 gene which result in the expression of various mutant or pathogenic forms of the KCNQ3 protein.

Selective modulators of Kv7 potassium channels that are useful for the treatment of a range of channelopathies, including epilepsy, developmental and epileptic encephalopathy, pain, tinnitus, cancer, cardiovascular disease, and neurodegeneration.

This article provides compounds, methods, and pharmaceutical compositions for reducing the amount or activity of SCN2A RNA in cells or subjects, and in some cases, reducing the amount of SCN2A protein in cells or subjects. Such compounds, methods, and pharmaceutical compositions can be used to improve at least one symptom or marker of a disease or disorder associated with voltage-gated sodium channel proteins, such as, for example, developmental and epileptic encephalopathy, intellectual disability, or autism spectrum disorder. Such symptoms and markers include, but are not limited to, seizures, hypotonia, sensory integration dysfunction, delayed and impaired motor development, intellectual and cognitive impairment, motor and balance impairment, visual impairment, language and speech delay, gastrointestinal disorders, delayed neurodevelopment, sleep problems, and sudden unexpected death in epilepsy.

Provided herein are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of SCN2A RNA, and in certain cases, the amount of SCN2A protein in a cell or subject. Such compounds, methods, and pharmaceutical compositions can be used to improve at least one symptom or indicia of a disease or disorder associated with a voltage-gated sodium channel protein, such as, for example, developmental and epileptic encephalopathies, intellectual disability, or an autism spectrum disorder. Such symptoms and indicia include, but are not limited to, seizures, hypotonia, sensory integration disorder, motor development delays and dysfunction, intellectual and cognitive dysfunction, motor and balance dysfunction, visual dysfunction, language and speech delays, gastrointestinal disorders, neurodevelopmental delays, sleep problems, and sudden unexpected death in epilepsy.

The present disclosure describes antisense oligonucleotides (ASOs) that target regions in a STXBP1 pre-mRNA. In certain embodiments, the ASOs are splice switching oligomers (SSOs) which target specific pre-mRNA splicing regulatory elements encoded in the STXBP1 gene and modify STXBP1 pre-mRNA splicing through steric blocking of the targeted splicing regulatory element. The present disclosure also describes methods for modifying the expression of Syntaxin binding protein 1 (STXBP1) using ASOs of the present disclosure. The present disclosure also describes methods of treating STXBP1 -related diseases, including developmental epileptic encephalopathy (DEE), by restoring canonical STXBP1 splicing and upregulating STXBP1 mRNA production using ASOs of the present disclosure.

To address most recurrent pathogenic mutations associated with SCN8A-related epileptic encephalopathy, disclosed herein are SCN8A-targeting adenine or cytosine base editors designed to correct the following clinically relevant SCN8A gene variants: R1872W, R1872Q, R1617Q, R850Q, N1877S, and G1475R. By targeting these six recurrent genetic mutations, a personalized gene therapy solution for this type of pediatric epilepsy is provided.

The present disclosure provides oligomeric compounds, methods and pharmaceutical compositions for reducing the amount or activity of methyl CpG binding protein 2 (MECP2) RNA and, in some cases, the amount of MECP2 protein in a cell or animal. Such oligomeric agents, oligomeric compounds, methods and pharmaceutical compositions are useful for improving at least one symptom or sign of a neurodevelopmental disease or condition. Such neurodevelopmental diseases or disorders include MECP2 repetition syndrome. Such symptoms or markers include autism, dyspepsia, dyskinesia, hypomyotonia, overall retardation of development, gastrointestinal symptoms, anxiety, epilepsy, recurrent respiratory tract infection, epileptic encephalopathy, and early death.

RNA interference-based methods and products for inhibiting the expression of pathogenic dynamin-1 variants are provided. Delivery vehicles such as recombinant adeno-associated viruses deliver DNAs encoding RNAs that inhibit the expression of the dynamin-1 variants. The methods treat, for example, developmental and epileptic encephalopathies.