Concise Review: Stem Cell Models of <i>SCN1A</i>-Related Encephalopathies—Current Perspective and Future Therapies
Mutations in the <i>SCN1A</i> gene can cause a variety of phenotypes, ranging from mild forms, such as febrile seizures and generalized epilepsy with febrile seizures plus, to severe, such as Dravet and non-Dravet developmental epileptic encephalopathies. Until now, more than two thousan...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/19/3119 |
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| author | Valery Zayat Roza Szlendak Dorota Hoffman-Zacharska |
| author_facet | Valery Zayat Roza Szlendak Dorota Hoffman-Zacharska |
| author_sort | Valery Zayat |
| collection | DOAJ |
| description | Mutations in the <i>SCN1A</i> gene can cause a variety of phenotypes, ranging from mild forms, such as febrile seizures and generalized epilepsy with febrile seizures plus, to severe, such as Dravet and non-Dravet developmental epileptic encephalopathies. Until now, more than two thousand pathogenic variants of the <i>SCN1A</i> gene have been identified and different pathogenic mechanisms (loss vs. gain of function) described, but the precise molecular mechanisms responsible for the deficits exhibited by patients are not fully elucidated. Additionally, the phenotypic variability proves the involvement of other genetic factors in its final expression. This is the reason why animal models and cell line models used to explore the molecular pathology of <i>SCN1A</i>-related disorders are only of limited use. The results of studies based on such models cannot be directly translated to affected individuals because they do not address each patient’s unique genetic background. The generation of functional neurons and glia for patient-derived iPSCs, together with the generation of isogenic controls using CRISPR/Cas technology, and finally, the 3D brain organoid models, seem to be a good way to solve this problem. Here, we review <i>SCN1A</i>-related encephalopathies, as well as the stem cell models used to explore their molecular basis. |
| first_indexed | 2024-03-09T21:52:36Z |
| format | Article |
| id | doaj.art-388f5fb2e04b495896de5cfb8ff54bd6 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T21:52:36Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-388f5fb2e04b495896de5cfb8ff54bd62023-11-23T20:03:08ZengMDPI AGCells2073-44092022-10-011119311910.3390/cells11193119Concise Review: Stem Cell Models of <i>SCN1A</i>-Related Encephalopathies—Current Perspective and Future TherapiesValery Zayat0Roza Szlendak1Dorota Hoffman-Zacharska2Department of Stem Cell Bioengineering, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02106 Warsaw, PolandMedical Genetics Department, Institute of Mother and Child, 01211 Warsaw, PolandMedical Genetics Department, Institute of Mother and Child, 01211 Warsaw, PolandMutations in the <i>SCN1A</i> gene can cause a variety of phenotypes, ranging from mild forms, such as febrile seizures and generalized epilepsy with febrile seizures plus, to severe, such as Dravet and non-Dravet developmental epileptic encephalopathies. Until now, more than two thousand pathogenic variants of the <i>SCN1A</i> gene have been identified and different pathogenic mechanisms (loss vs. gain of function) described, but the precise molecular mechanisms responsible for the deficits exhibited by patients are not fully elucidated. Additionally, the phenotypic variability proves the involvement of other genetic factors in its final expression. This is the reason why animal models and cell line models used to explore the molecular pathology of <i>SCN1A</i>-related disorders are only of limited use. The results of studies based on such models cannot be directly translated to affected individuals because they do not address each patient’s unique genetic background. The generation of functional neurons and glia for patient-derived iPSCs, together with the generation of isogenic controls using CRISPR/Cas technology, and finally, the 3D brain organoid models, seem to be a good way to solve this problem. Here, we review <i>SCN1A</i>-related encephalopathies, as well as the stem cell models used to explore their molecular basis.https://www.mdpi.com/2073-4409/11/19/3119<i>SCN1A</i>-related disordersdevelopmental and epileptic encephalopathiesNav1.1functional studiesstem cell modelsorganoids |
| spellingShingle | Valery Zayat Roza Szlendak Dorota Hoffman-Zacharska Concise Review: Stem Cell Models of <i>SCN1A</i>-Related Encephalopathies—Current Perspective and Future Therapies Cells <i>SCN1A</i>-related disorders developmental and epileptic encephalopathies Nav1.1 functional studies stem cell models organoids |
| title | Concise Review: Stem Cell Models of <i>SCN1A</i>-Related Encephalopathies—Current Perspective and Future Therapies |
| title_full | Concise Review: Stem Cell Models of <i>SCN1A</i>-Related Encephalopathies—Current Perspective and Future Therapies |
| title_fullStr | Concise Review: Stem Cell Models of <i>SCN1A</i>-Related Encephalopathies—Current Perspective and Future Therapies |
| title_full_unstemmed | Concise Review: Stem Cell Models of <i>SCN1A</i>-Related Encephalopathies—Current Perspective and Future Therapies |
| title_short | Concise Review: Stem Cell Models of <i>SCN1A</i>-Related Encephalopathies—Current Perspective and Future Therapies |
| title_sort | concise review stem cell models of i scn1a i related encephalopathies current perspective and future therapies |
| topic | <i>SCN1A</i>-related disorders developmental and epileptic encephalopathies Nav1.1 functional studies stem cell models organoids |
| url | https://www.mdpi.com/2073-4409/11/19/3119 |
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