Haploinsufficiency, Dominant Negative, and Gain-of-Function Mechanisms in Epilepsy: Matching Therapeutic Approach to the Pathophysiology
| Autor: | Gemma L. Carvill, Tyler Matheny, Scott Demarest, Jay R. Hesselberth |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Neurology Genetic enhancement Haploinsufficiency Review Therapeutic approach Epilepsy Genome editing medicine Humans Pharmacology (medical) Precision Medicine Gene Editing Pharmacology business.industry Mechanism (biology) Genetic Therapy Oligonucleotides Antisense medicine.disease Null allele Gain of Function Mutation Neurology (clinical) business Neuroscience |
| Zdroj: | Neurotherapeutics |
| ISSN: | 1878-7479 1933-7213 |
| DOI: | 10.1007/s13311-021-01137-z |
| Popis: | This review summarizes the pathogenic mechanisms that underpin the monogenic epilepsies and discusses the potential of novel precision therapeutics to treat these disorders. Pathogenic mechanisms of epilepsy include recessive (null alleles), haploinsufficiency, imprinting, gain-of-function, and dominant negative effects. Understanding which pathogenic mechanism(s) that underlie each genetic epilepsy is pivotal to design precision therapies that are most likely to be beneficial for the patient. Novel therapeutics discussed include gene therapy, gene editing, antisense oligonucleotides, and protein replacement. Discussions are illustrated and reinforced with examples from the literature. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-021-01137-z. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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