Title
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STXBP1 as a therapeutic target for epileptic encephalopathy
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Author
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Abstract
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Introduction: STXBP1 is an essential protein for presynaptic vesicle release. Mutations in STXBP1 have been associated with a series of (epileptic) neurodevelopmental disorders collectively referred to as STXBP1-encephalopathy (STXBP1-E). In this review we hypothesize about the potential of STXBP1 as a therapeutic target in the field of epileptic encephalopathies. Areas covered: A state of the art overview on current understanding of the pathophysiologic mechanism underlying STXBP1-E is presented. Possibilities of different treatment modalities are discussed including unbiased compound screening, specific protein-protein interaction inhibition and gene therapy, consisting either of gene suppletion or upregulation of gene expression. Expert opinion: Current treatment for STXBP1-E is largely limited to seizure control and future therapies will need to target the developmental aspects of the disease as well. Both in vitro- and animal models used to study the pathophysiology of STXBP1-E could be further optimized as a model for compound screening. They should reflect both the hyper excitable state and the psychomotor delay of STXBP1-E. Specific protein-protein interaction and gene therapy are promising future treatment options that need to be investigated further. We suggest a parallel research strategy on basic pathophysiology and compound development with both fields working in close collaboration with the patient/clinical community. KEYWORDS: Epileptic encephalopathy, MUNC18-1, neurodevelopmental disorder, precision medicine, STXBP1, therapeutic target |
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Language
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English
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Source (journal)
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Expert opinion on therapeutic targets. - London
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Publication
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Abingdon
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Taylor & francis ltd
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2017
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ISSN
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1472-8222
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DOI
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10.1080/14728222.2017.1386175
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Volume/pages
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21
:11
(2017)
, p. 1027-1036
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ISI
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000414547300004
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Pubmed ID
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28971703
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Full text (Publisher's DOI)
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