{"title":"Seizure-suppressor genes: can they help spearhead the discovery of novel therapeutic targets for epilepsy?","authors":"Gleice Kelli Silva-Cardoso, Prosper N'Gouemo","doi":"10.1080/14728222.2023.2248375","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Epilepsies are disorders of neuronal excitability characterized by spontaneously recurrent focal and generalized seizures, some of which result from genetic mutations. Despite the availability of antiseizure medications, pharmaco-resistant epilepsy is seen in about 23% of epileptic patients worldwide. Therefore, there is an urgent need to develop novel therapeutic strategies for epilepsies. Several epilepsy-associated genes have been found in humans. Seizure susceptibility can also be induced in <i>Drosophila</i> mutants, some showing features resembling human epilepsies. Interestingly, several second-site mutation gene products have been found to suppress seizure susceptibility in the seizure genetic model <i>Drosophila</i>. Thus, these so-called 'seizure-suppressor' gene variants may lead to developing a novel class of antiseizure medications.</p><p><strong>Area covered: </strong>This review evaluates the potential therapeutic of seizure-suppressor gene variants.</p><p><strong>Expert opinion: </strong>Studies on epilepsy-associated genes have allowed analyses of mutations linked to human epilepsy by reproducing these mutations in <i>Drosophila</i> using reverse genetics to generate potential antiseizure therapeutics. As a result, about fifteen seizure-suppressor gene mutants have been identified. Furthermore, some of these epilepsy gene mutations affect ligand-and voltage-gated ion channels. Therefore, a better understanding of the antiseizure activity of seizure-suppressor genes is essential in advancing gene therapy and precision medicine for epilepsy.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10528013/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Opinion on Therapeutic Targets","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/14728222.2023.2248375","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/8/22 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Epilepsies are disorders of neuronal excitability characterized by spontaneously recurrent focal and generalized seizures, some of which result from genetic mutations. Despite the availability of antiseizure medications, pharmaco-resistant epilepsy is seen in about 23% of epileptic patients worldwide. Therefore, there is an urgent need to develop novel therapeutic strategies for epilepsies. Several epilepsy-associated genes have been found in humans. Seizure susceptibility can also be induced in Drosophila mutants, some showing features resembling human epilepsies. Interestingly, several second-site mutation gene products have been found to suppress seizure susceptibility in the seizure genetic model Drosophila. Thus, these so-called 'seizure-suppressor' gene variants may lead to developing a novel class of antiseizure medications.
Area covered: This review evaluates the potential therapeutic of seizure-suppressor gene variants.
Expert opinion: Studies on epilepsy-associated genes have allowed analyses of mutations linked to human epilepsy by reproducing these mutations in Drosophila using reverse genetics to generate potential antiseizure therapeutics. As a result, about fifteen seizure-suppressor gene mutants have been identified. Furthermore, some of these epilepsy gene mutations affect ligand-and voltage-gated ion channels. Therefore, a better understanding of the antiseizure activity of seizure-suppressor genes is essential in advancing gene therapy and precision medicine for epilepsy.
期刊介绍:
The journal evaluates molecules, signalling pathways, receptors and other therapeutic targets and their potential as candidates for drug development. Articles in this journal focus on the molecular level and early preclinical studies. Articles should not include clinical information including specific drugs and clinical trials.
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Reviews covering novel disease targets at the molecular level and information on early preclinical studies and their implications for future drug development.
Articles should not include clinical information including specific drugs and clinical trials.
Original research papers reporting results of target selection and validation studies and basic mechanism of action studies for investigative and marketed drugs.
The audience consists of scientists, managers and decision makers in the pharmaceutical industry, academic researchers working in the field of molecular medicine and others closely involved in R&D.