A5011062761- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Epilepsy research and treatment
- Iron Metabolism and Disorders
- Trace Elements in Health
- Hemoglobinopathies and Related Disorders
- Cardiac electrophysiology and arrhythmias
- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Heavy Metal Exposure and Toxicity
- Genomic variations and chromosomal abnormalities
- RNA regulation and disease
- Pain Mechanisms and Treatments
- Metabolism and Genetic Disorders
- Diet and metabolism studies
- Neuroscience and Neural Engineering
Xenon Pharmaceuticals (Canada)
2011-2024
Johns Hopkins Medicine
2021
Johns Hopkins University
2021
NBI-921352 (formerly XEN901) is a novel sodium channel inhibitor designed to specifically target NaV1.6 channels. Such molecule provides precision-medicine approach SCN8A-related epilepsy syndromes (SCN8A-RES), where gain-of-function (GoF) mutations lead excess current, or other indications mediated hyper-excitability contributes disease (Gardella and Møller, 2019; Johannesen et al., Veeramah 2012). potent of (IC500.051 µM), with exquisite selectivity over isoforms (selectivity ratios 756 X...
Voltage-gated sodium channel (NaV) mutations cause genetic pain disorders that range from severe paroxysmal to a congenital inability sense pain. Previous studies on NaV1.7 and NaV1.8 established clear relationships between perturbations in function divergent clinical phenotypes. By contrast, of NaV1.9 have not revealed relationship dysfunction with the associated contrasting Here, we elucidated functional consequences mutation (L1302F) is insensitivity We investigated effects L1302F...
Background and Purpose Inhibitors of voltage‐gated sodium channels (Na V s) are important anti‐epileptic drugs, but the contribution specific channel isoforms is unknown since available inhibitors non‐selective. We aimed to create novel, isoform selective Na v as a means informing development improved antiseizure drugs. Experimental Approach created series compounds with diverse selectivity profiles enabling block 1.6 alone or together 1.2. These novel were evaluated for their ability...
SCN8A developmental epileptic encephalopathy (SCN8A-DEE) is a rare and severe genetic epilepsy syndrome characterized by early-onset delay, cognitive impairment, intractable seizures. gene variants are associated with broad phenotypic spectrum variable disease severity. A caregiver survey, solicited the advocacy group The Cute Syndrome Foundation (TCSF), was conducted to gather information on demographics/disease presentation, seizure history, treatment of patients SCN8A-related epilepsies.A...
Divalent metal transporter 1 (DMT1) cotransports ferrous iron and protons is the primary mechanism for uptake of nonheme by enterocytes. Inhibitors are potentially useful as therapeutic agents to treat overload disorders such hereditary hemochromatosis or β-thalassemia intermedia, provided that inhibition can be restricted duodenum. We used a calcein quench assay identify human DMT1 (hDMT1) inhibitors. Dimeric compounds were made generate more potent with low systemic exposure. Direct block...
Abstract Inhibitors of voltage-gated sodium channels (Na V s) are important anti-epileptic drugs, but the contribution specific channel isoforms is unknown since available inhibitors nonselective. We created a series compounds with diverse selectivity profiles enabling block Na 1.6 alone or together 1.2. Mice heterozygous gain-of-function mutation (N1768D/+) in Scn8a (encoding 1.6) responded tonic-clonic seizure to mild 6 Hz stimulus that was innocuous wild-type mice. Pharmacologic...
Abstract Voltage-gated sodium ion channels allow for the initiation and transmission of action potentials. There is a high interest in research drug development to selectively target these treat epilepsy other disorders such as pain. Scientific literature presentations often incorporate maps integral membrane proteins with markers indicating gene mutations highlight genotype/phenotype correlations. need automated tools create quality figures mutation (variant) locations displayed on channel...
ABSTRACT Divalent metal transporter 1 (DMT1) cotransports ferrous iron and protons is the primary mechanism for uptake of non-heme by enterocytes. Inhibitors are potentially useful as therapeutic agents to treat overload disorders such hereditary hemochromatosis or β-thalassemia intermedia, provided that inhibition can be restricted duodenum. We used a calcein quench assay identify human DMT1 (hDMT1) inhibitors. Dimeric constructs were made generate more potent compounds with low systemic...
Abstract NBI-921352 (formerly XEN901) is a novel sodium channel inhibitor designed to specifically target Na V 1.6 channels. Such molecule provides precision-medicine approach SCN8A -related epilepsy syndromes ( -RES), where gain-of-function (GoF) mutations lead excess current, or other indications mediated hyper-excitability contributes disease (Gardella and Moller, 2019; Johannesen et al., Veeramah 2012). potent of (IC 50 0.051 µM), with exquisite selectivity over isoforms (selectivity...
ABSTRACT Purpose SCN8A developmental epileptic encephalopathy (SCN8A-DEE) is a rare and severe genetic epilepsy syndrome characterized by early-onset delay, cognitive impairment, intractable seizures. Variants in the gene are associated with broad phenotypic spectrum variable disease severity. A caregiver survey, solicited advocacy group The Cute Syndrome Foundation (TCSF), was conducted to gather information on demographics/disease presentation, seizure history, treatment of patients...