Human Epilepsy Models
Epilepsy, an emergence in uncontrolled electrical activity in the brain, affects ~65 million individuals globally. Over one-third of clinically diagnosed with epilepsy struggle to control seizures through pharmacological treatments. Epilepsy has countless developmental and genetic etiologies, including single-gene mutations within ion channels that regulate neuronal activity and function. Human neurons derived from induced pluripotent stem cells (iPSCs) are emerging as a more biologically relevant and predictive cellular model for discovery and pre-clinical phases of drug development.
Engineered Epilepsy Models
What is an engineered model and its benefits?
Engineering of epilepsy-associated mutations into human iPSCs enables creation of relevant and accessible neural cell culture models to study. Our selection of engineered iCell GABANeurons offer an off-the-shelf and consistent source of cells to model Dravet syndrome, febrile seizures, and autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE).
KCNT1P924L
KCNT1P924L is a gain of function mutation within the sodium-activated potassium channel (Slack, KNa1). This mutation is associated with malignant migrating partial seizures of infancy (MMPSI) and autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE).
Cell Line Options:
SCN1A HZ Knockout
Mutations in the SCN1A gene, encoding the voltage-gated sodium channel Nav1.1 alpha subunit, is associated with multiple epilepsy conditions including Dravet syndrome (severe myoclonic epilepsy of infancy) and febrile seizures Plus (GEFS+).
Cell Line Options:
Induced Seizurogenic Models
Combining iCell GlutaNeurons, iCell Astrocytes, or iCell GABANeurons in culture offers a novel, accessible and human-relevant method for creating iPSC-derived “Epilepsy-in-a-dish” models. These models are being adopted by neurotoxicity consortiums, like NeuroDeRisk and NeuTox, to develop standards for high-throughput epilepsy drug screening and increase drug pipeline translatability, compared to traditional primary rodent cultures.
Benefits of iCell "Epilepsy-in-a-dish" models
- iCell GlutaNeurons and iCell Astrocytes form baseline model
- Assay network activity by ~21 days in culture
- Induce seizurogenic activity using compounds
- Customize inhibitory/excitatory by adjusting iCell ratios
- Easily incorporate engineered epilepsy iCell GABANeuron
iCell® NeuroSpheres
3D in vitro models of the brain continue to advance the predictive power of cellular models for epilepsy drug discovery. Despite years of use in the field, 3D models still have challenges including model consistency, assay accessibility, and flexibility for making disease models. iCell NeuroSpheres offer a solution to these challenges. Combine iCell GlutaNeurons with iCell Astrocytes and iCell GABANeurons to generate seizurogenic models.
- Uses off-the-shelf iCell neuronal and glial cells
- Generates reproducible sphere size and cell type ratios
- Incorporate KCNT1 and SCN1A iCell GABANeurons for epilepsy modeling
- Generates one sphere per well in a 384-well format
Need a custom iPSC-derived cell model for epilepsy?
Contact us to discuss custom projects using your donor cells or alternate neural cell types available with our current epilepsy cell line models.
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