Gene Therapy: Novel Approaches to Targeting Monogenic Epilepsies
Genetic epilepsies are a spectrum of disorders characterized by spontaneous and recurrent seizures that can arise from an array of inherited or de novo genetic variants and disrupt normal brain development or neuronal connectivity and function. Genetically determined epilepsies, many of which are du...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2022.805007/full |
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| author | Kimberly Goodspeed Rachel M. Bailey Rachel M. Bailey Suyash Prasad Chanchal Sadhu Jessica A. Cardenas Mary Holmay Deborah A. Bilder Berge A. Minassian |
| author_facet | Kimberly Goodspeed Rachel M. Bailey Rachel M. Bailey Suyash Prasad Chanchal Sadhu Jessica A. Cardenas Mary Holmay Deborah A. Bilder Berge A. Minassian |
| author_sort | Kimberly Goodspeed |
| collection | DOAJ |
| description | Genetic epilepsies are a spectrum of disorders characterized by spontaneous and recurrent seizures that can arise from an array of inherited or de novo genetic variants and disrupt normal brain development or neuronal connectivity and function. Genetically determined epilepsies, many of which are due to monogenic pathogenic variants, can result in early mortality and may present in isolation or be accompanied by neurodevelopmental disability. Despite the availability of more than 20 antiseizure medications, many patients with epilepsy fail to achieve seizure control with current therapies. Patients with refractory epilepsy—particularly of childhood onset—experience increased risk for severe disability and premature death. Further, available medications inadequately address the comorbid developmental disability. The advent of next-generation gene sequencing has uncovered genetic etiologies and revolutionized diagnostic practices for many epilepsies. Advances in the field of gene therapy also present the opportunity to address the underlying mechanism of monogenic epilepsies, many of which have only recently been described due to advances in precision medicine and biology. To bring precision medicine and genetic therapies closer to clinical applications, experimental animal models are needed that replicate human disease and reflect the complexities of these disorders. Additionally, identifying and characterizing clinical phenotypes, natural disease course, and meaningful outcome measures from epileptic and neurodevelopmental perspectives are necessary to evaluate therapies in clinical studies. Here, we discuss the range of genetically determined epilepsies, the existing challenges to effective clinical management, and the potential role gene therapy may play in transforming treatment options available for these conditions. |
| first_indexed | 2024-04-13T14:46:07Z |
| format | Article |
| id | doaj.art-8054f1b9a6694137b846ce2c06b7d5ae |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-04-13T14:46:07Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-8054f1b9a6694137b846ce2c06b7d5ae2022-12-22T02:42:44ZengFrontiers Media S.A.Frontiers in Neurology1664-22952022-06-011310.3389/fneur.2022.805007805007Gene Therapy: Novel Approaches to Targeting Monogenic EpilepsiesKimberly Goodspeed0Rachel M. Bailey1Rachel M. Bailey2Suyash Prasad3Chanchal Sadhu4Jessica A. Cardenas5Mary Holmay6Deborah A. Bilder7Berge A. Minassian8Division of Child Neurology, Department of Pediatrics, University of Texas Southwestern, Dallas, TX, United StatesDivision of Child Neurology, Department of Pediatrics, University of Texas Southwestern, Dallas, TX, United StatesCenter for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern, Dallas, TX, United StatesDepartment of Research and Development, Taysha Gene Therapies, Dallas, TX, United StatesDepartment of Research and Development, Taysha Gene Therapies, Dallas, TX, United StatesDepartment of Research and Development, Taysha Gene Therapies, Dallas, TX, United StatesDepartment of Research and Development, Taysha Gene Therapies, Dallas, TX, United StatesDivision of Child and Adolescent Psychiatry, Department of Psychiatry, Huntsman Mental Health Institute, University of Utah, Salt Lake City, UT, United StatesDivision of Child Neurology, Department of Pediatrics, University of Texas Southwestern, Dallas, TX, United StatesGenetic epilepsies are a spectrum of disorders characterized by spontaneous and recurrent seizures that can arise from an array of inherited or de novo genetic variants and disrupt normal brain development or neuronal connectivity and function. Genetically determined epilepsies, many of which are due to monogenic pathogenic variants, can result in early mortality and may present in isolation or be accompanied by neurodevelopmental disability. Despite the availability of more than 20 antiseizure medications, many patients with epilepsy fail to achieve seizure control with current therapies. Patients with refractory epilepsy—particularly of childhood onset—experience increased risk for severe disability and premature death. Further, available medications inadequately address the comorbid developmental disability. The advent of next-generation gene sequencing has uncovered genetic etiologies and revolutionized diagnostic practices for many epilepsies. Advances in the field of gene therapy also present the opportunity to address the underlying mechanism of monogenic epilepsies, many of which have only recently been described due to advances in precision medicine and biology. To bring precision medicine and genetic therapies closer to clinical applications, experimental animal models are needed that replicate human disease and reflect the complexities of these disorders. Additionally, identifying and characterizing clinical phenotypes, natural disease course, and meaningful outcome measures from epileptic and neurodevelopmental perspectives are necessary to evaluate therapies in clinical studies. Here, we discuss the range of genetically determined epilepsies, the existing challenges to effective clinical management, and the potential role gene therapy may play in transforming treatment options available for these conditions.https://www.frontiersin.org/articles/10.3389/fneur.2022.805007/fullgenetic epilepsyAAV9LaforaSLC13A5SLC6A1gene therapy (GT) |
| spellingShingle | Kimberly Goodspeed Rachel M. Bailey Rachel M. Bailey Suyash Prasad Chanchal Sadhu Jessica A. Cardenas Mary Holmay Deborah A. Bilder Berge A. Minassian Gene Therapy: Novel Approaches to Targeting Monogenic Epilepsies Frontiers in Neurology genetic epilepsy AAV9 Lafora SLC13A5 SLC6A1 gene therapy (GT) |
| title | Gene Therapy: Novel Approaches to Targeting Monogenic Epilepsies |
| title_full | Gene Therapy: Novel Approaches to Targeting Monogenic Epilepsies |
| title_fullStr | Gene Therapy: Novel Approaches to Targeting Monogenic Epilepsies |
| title_full_unstemmed | Gene Therapy: Novel Approaches to Targeting Monogenic Epilepsies |
| title_short | Gene Therapy: Novel Approaches to Targeting Monogenic Epilepsies |
| title_sort | gene therapy novel approaches to targeting monogenic epilepsies |
| topic | genetic epilepsy AAV9 Lafora SLC13A5 SLC6A1 gene therapy (GT) |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2022.805007/full |
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