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.

Abstract: A method for the diagnosis of SMEI in a patient comprising: (1) detecting an alteration in the SCN1A gene, including in a regulatory region of the gene, in a patient sample; (2) ascertaining whether the alteration is known to be SMEI associated or non-SMEI associated; and (3) (a) establishing a diagnosis of a high probability of SMEI where the alteration is known to be SMEI associated; or (b) establishing a diagnosis of a low probability of SMEI where the alteration is non-SMEI associated; or (e) or, if not known to be either, (i) considering genetic data for parents and/or relatives; (ii) establishing whether the alteration has arisen de novo or is inherited; and (iii) establishing a diagnosis of a low probability of SMEI where the alteration is inherited but a diagnosis of a high probability of SMEI if the alteration is de novo.

Abstract: This invention relates to a method of assaying a compound for its ability to modulate an ion channel or receptor type, the method comprising: a) providing a dynamic clamp in electrical contact with a biological cell (or part thereof) in which one or more ion channel or receptor types for providing a waveform are functional and in which one or more ion channel or receptor types for providing a waveform are either not present or not functional; b) causing the dynamic clamp to apply a signal simulating the function of at least one of the one or more ion channel or receptor types that are either not present or not functional in the biological cell (or part thereof) based on modulation of the ion channel or receptor types that are functional in the biological cell (or part thereof) to thereby provide the waveform at the biological cell (or part thereof); c) exposing at least one of the one or more functional ion channel or receptor types to a compound; and d) detecting modulation of the waveform at the biological

Abstract: A method for the diagnosis of SMEI in a patient comprising: (1) detecting an alteration in the SCN1A gene, including in a regulatory region of the gene, in a patient sample; (2) ascertaining whether the alteration is known to be SMEI associated or non-SMEI associated; and (3) (a) establishing a diagnosis of a high probability of SMEI where the alteration is known to be SMEI associated; or (b) establishing a diagnosis of a low probability of SMEI where the alteration is non-SMEI associated; or (e) or, if not known to be either, (i) considering genetic data for parents and/or relatives; (ii) establishing whether the alteration has arisen de novo or is inherited; and (iii) establishing a diagnosis of a low probability of SMEI where the alteration is inherited but a diagnosis of a high probability of SMEI if the alteration is de novo.

Abstract: The description discloses that amiloride-like compounds inhibit enterovirus RNA replication by interaction with RNA dependent RNA polymerase (RdRP). The description discloses in silico and in vitro methods of screening for inhibitors of RdRP activity, amiloride-resistant enterovirus variants and amiloride-like compounds.

Abstract: A method for the diagnosis of SMEI in a patient comprising: (1) detecting an alteration in the SCN1A gene, including in a regulatory region of the gene, in a patient sample; (2) ascertaining whether the alteration is known to be SMEI associated or non-SMEI associated; and (3) (a) establishing a diagnosis of a high probability of SMEI where the alteration is known to be SMEI associated; or (b) establishing a diagnosis of a low probability of SMEI where the alteration is non-SMEI associated; or (e) or, if not known to be either, (i) considering genetic data for parents and/or relatives; (ii) establishing whether the alteration has arisen de novo or is inherited; and (iii) establishing a diagnosis of a low probability of SMEI where the alteration is inherited but a diagnosis of a high probability of SMEI if the alteration is de novo.

Abstract: A method for the diagnosis of an epilepsy syndrome, including SMEI or an SMEI-related syndrome, in a patient comprising testing for an alteration in the SCN1A gene in a sample obtained from the patient; and if an alteration is identified, comparing said alteration to any one of those listed in Table 3, wherein if said alteration is identical to any one of those listed in Table 3, a diagnosis of an epilepsy syndrome, including SMEI or an SMEI-related syndrome, in said patient is made in accordance with the correlation set forth in Table 3.

Abstract: A method for the diagnosis of SMEI in a patient comprising: