Abstract: The present disclosure relates to methods of treating essential tremor that comprise administering to a subject in need thereof compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I), or a pharmaceutically acceptable salt thereof, is administered to the subject once daily at a dose of about 20 mg to about 60 mg; such that The Essential Tremor Rating Assessment Scale (TETRAS) performance score of said subject is decreased by at least 3 points following administration of the compound of formula (I), or a pharmaceutically acceptable salt thereof, as compared to the TETRAS performance score of said subject prior to the administration of the compound of formula (I), or a pharmaceutically acceptable salt thereof.

Abstract: Provided herein are methods, compounds, and compositions for reducing expression of SCN2A in a subject. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate an SCN1A related disease or disorder (e.g., Dravet syndrome) in a subject in need.

Abstract: The present invention provides methods for determining the phenotype (e.g., gain-of-function or loss-of-function) of a mutation in an ion channel or receptor by using a dynamic voltage clamp. The invention also features methods of determining whether a mutation is a gain-of-function or loss- of-function mutation and treating a disease or disorder associated with the particular gain-of-function or loss-of-function mutation.

Abstract: The disclosure relates to methods of treating a neurological disorder, such as epilepsy or an epilepsy syndrome, with Compound 1 or pharmaceutically acceptable salts thereof, alone, or in combination with sodium ion (Na+) channel blockers.

Abstract: 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.

Abstract: The present invention provides methods for determining the phenotype (e.g., gain-of-function or loss-of-function) of a mutation in an ion channel or receptor by using a dynamic voltage clamp. The invention also features methods of determining whether a mutation is a gain-of-function or loss-of-function mutation and treating a disease or disorder associated with the particular gain-of-function or loss-of-function mutation.

Abstract: Provided herein are antisense oligonucleotides to a target region of the protocadherin 19 (PCDH19) gene. The antisense oligonucleotides or compositions comprising same may be administered to a subject with a PCDH19 related disorder, such as epilepsy, schizophrenia or autism, in order to treat, reduce the symptoms of, or prevent the PCDH19 related disorder. Accordingly, also provided herein are useful compositions and methods to treat PCDH19 related disorders.

Abstract: Provided herein are methods, compounds, and compositions for reducing expression of SCN2A in a subject. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate an SCN1A related disease or disorder (e.g., Dravet syndrome) in a subject in need.

Abstract: Provided herein are methods, compounds, and compositions for reducing expression of sodium voltage-gated channel alpha subunit 2 (SCN2A) in a subject. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate a sodium voltage gated channel alpha subunit 1 (SCN1A) related disease or disorder (e.g., Dravet syndrome) in a subject in need.

Abstract: Provided herein are methods for increasing levels of SCN2A protein in a cell, comprising contacting the cell with an antisense oligonucleotide that enhances splicing at a splice site of a retained intron in an intron-retaining SCN2A mRNA or pre-mRNA, wherein the retained intron is selected from among intron 1, 2, 3, 4, 5, 11, 13, 17 and 24 and wherein the antisense oligonucleotide comprises a sequence of nucleobases that is complementary to a target region in the SCN2A mRNA or pre-mRNA. Also provided are antisense oligonucleotides for use in such methods. Also provided are methods for treating disorders associated with a heterozygous loss-of-function mutation in SCN2A, comprising administering to the subject such antisense oligonucleotides.

Abstract: Described herein are compositions and methods that are used to increase the expression of SCN2A, which may be used to treat neurological or psychiatric disorders. Antisense oligonucleotides that target upstream open reading frames (uORFs) may be administered to prevent translation initiation from a uORF to increase expression from a primary ORF (pORF), thus increasing the levels of SCN2A protein.

Abstract: The present disclosure relates generally to compositions and methods suitable for treating a disorder associated with loss-of-function mutations in SYNGAP1. More specifically, the disclosure relates to methods for treating a disorder associated with heterozygous loss-of-function mutations of SYNGAP1, and to antisense oligonucleotides specific for SYNGAP1 and their use for treating a disorder associated with heterozygous loss-of-function mutations of SYNGAP1.

Abstract: Methods, compounds, and compositions for increasing expression of voltage-gated, Sodium Channel Alpha Subunit 2 (SCN2A) in a subject. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate an SCN2A related disease or disorder (e.g., SCN2A encephalopathy) or autism in a subject in need.

Abstract: The present disclosure features useful compositions and methods to treat KCNT1 related disorders, e.g., in a subject in need thereof.

Abstract: Described herein are compositions and methods that are used to increase the expression of SCN2A, which may be used to treat neurological or psychiatric disorders. Antisense oligonucleotides that target upstream open reading frames (uORFs) may be administered to prevent translation initiation from a uORF to increase expression from a primary ORF (pORF), thus increasing the levels of SCN2A protein.

Abstract: Provided herein are methods, compounds, and compositions for reducing expression of sodium voltage-gated channel alpha subunit 2 (SCN2A) in a subject. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate a sodium voltage gated channel alpha subunit 1 (SCN1A) related disease or disorder (e.g., Dravet syndrome) in a subject in need.

Abstract: This invention relates to peptides and their use for modulating sodium channels. More particularly, the present invention relates to peptides and their use in methods of enhancing Nav1.1 activity and for treating or preventing conditions associated with Nav1.1 activity.

Abstract: The present invention provides methods for determining the phenotype (e.g., gain-of-function or loss-of-function) of a mutation in an ion channel or receptor by using a dynamic voltage clamp. The invention also features methods of determining whether a mutation is a gain-of-function or loss-of-function mutation and treating a disease or disorder associated with the particular gain-of-function or loss-of-function mutation.

Abstract: This invention relates to peptides and their use for modulating sodium channels. More particularly, the present invention relates to peptides and their use in methods of enhancing Nav1.1 activity and for treating or preventing conditions associated with Nav1.1 activity.

Abstract: Compositions and methods suitable for treating diseases and conditions associated excessive neuronal excitability, and/or diseases associated with gain-of-function mutations in KCNT1. More specifically, antisense oligonucleotides specific for KCNT1 and their use for treating diseases and conditions associated with excessive neuronal excitability and/or gain-of-function mutations of KCNT1.