New developments in the management of narcolepsy

Vivien C Abad, Christian Guilleminault Department of Psychiatry and Behavioral Sciences, Division of Sleep Medicine, Stanford University Outpatient Center, Redwood City, CA, USA Abstract: Narcolepsy is a life-long, underrecognized sleep disorder that affects 0.02%–0.18% of the US...

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Autores principales:	Abad VC, Guilleminault C
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	narcolepsy cataplexy emerging treatment sodium oxybate pitolisant JZP-110 hypocretin peptide immunotherapy Psychiatry RC435-571 Neurophysiology and neuropsychology QP351-495
Acceso en línea:	https://doaj.org/article/b15a6738adbc4be08828fb343f6c8a93
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spelling	oai:doaj.org-article:b15a6738adbc4be08828fb343f6c8a932021-12-02T03:30:32ZNew developments in the management of narcolepsy1179-1608https://doaj.org/article/b15a6738adbc4be08828fb343f6c8a932017-03-01T00:00:00Zhttps://www.dovepress.com/new-developments-in-the-management-of-narcolepsy-peer-reviewed-article-NSShttps://doaj.org/toc/1179-1608Vivien C Abad, Christian Guilleminault Department of Psychiatry and Behavioral Sciences, Division of Sleep Medicine, Stanford University Outpatient Center, Redwood City, CA, USA Abstract: Narcolepsy is a life-long, underrecognized sleep disorder that affects 0.02%–0.18% of the US and Western European populations. Genetic predisposition is suspected because of narcolepsy’s strong association with HLA DQB1*06-02, and genome-wide association studies have identified polymorphisms in T-cell receptor loci. Narcolepsy pathophysiology is linked to loss of signaling by hypocretin-producing neurons; an autoimmune etiology possibly triggered by some environmental agent may precipitate hypocretin neuronal loss. Current treatment modalities alleviate the main symptoms of excessive daytime somnolence (EDS) and cataplexy and, to a lesser extent, reduce nocturnal sleep disruption, hypnagogic hallucinations, and sleep paralysis. Sodium oxybate (SXB), a sodium salt of γ hydroxybutyric acid, is a first-line agent for cataplexy and EDS and may help sleep disruption, hypnagogic hallucinations, and sleep paralysis. Various antidepressant medications including norepinephrine serotonin reuptake inhibitors, selective serotonin reuptake inhibitors, and tricyclic antidepressants are second-line agents for treating cataplexy. In addition to SXB, modafinil and armodafinil are first-line agents to treat EDS. Second-line agents for EDS are stimulants such as methylphenidate and extended-release amphetamines. Emerging therapies include non-hypocretin-based therapy, hypocretin-based treatments, and immunotherapy to prevent hypocretin neuronal death. Non-hypocretin-based novel treatments for narcolepsy include pitolisant (BF2.649, tiprolisant); JZP-110 (ADX-N05) for EDS in adults; JZP 13-005 for children; JZP-386, a deuterated sodium oxybate oral suspension; FT 218 an extended-release formulation of SXB; and JNJ-17216498, a new formulation of modafinil. Clinical trials are investigating efficacy and safety of SXB, modafinil, and armodafinil in children. γ-amino butyric acid (GABA) modulation with GABAA receptor agonists clarithromycin and flumazenil may help daytime somnolence. Other drugs investigated include GABAB agonists (baclofen), melanin-concentrating hormone antagonist, and thyrotropin-releasing hormone agonists. Hypocretin-based therapies include hypocretin peptide replacement administered either through an intracerebroventricular route or intranasal route. Hypocretin neuronal transplant and transforming stem cells into hypothalamic neurons are also discussed in this article. Immunotherapy to prevent hypocretin neuronal death is reviewed. Keywords: narcolepsy, cataplexy, emerging treatment, sodium oxybate, pitolisant, JZP-110, hypocretin peptide, immunotherapy Abad VCGuilleminault CDove Medical Pressarticlenarcolepsycataplexyemerging treatmentsodium oxybatepitolisantJZP-110hypocretin peptideimmunotherapyPsychiatryRC435-571Neurophysiology and neuropsychologyQP351-495ENNature and Science of Sleep, Vol Volume 9, Pp 39-57 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	narcolepsy cataplexy emerging treatment sodium oxybate pitolisant JZP-110 hypocretin peptide immunotherapy Psychiatry RC435-571 Neurophysiology and neuropsychology QP351-495
spellingShingle	narcolepsy cataplexy emerging treatment sodium oxybate pitolisant JZP-110 hypocretin peptide immunotherapy Psychiatry RC435-571 Neurophysiology and neuropsychology QP351-495 Abad VC Guilleminault C New developments in the management of narcolepsy
description	Vivien C Abad, Christian Guilleminault Department of Psychiatry and Behavioral Sciences, Division of Sleep Medicine, Stanford University Outpatient Center, Redwood City, CA, USA Abstract: Narcolepsy is a life-long, underrecognized sleep disorder that affects 0.02%–0.18% of the US and Western European populations. Genetic predisposition is suspected because of narcolepsy’s strong association with HLA DQB1*06-02, and genome-wide association studies have identified polymorphisms in T-cell receptor loci. Narcolepsy pathophysiology is linked to loss of signaling by hypocretin-producing neurons; an autoimmune etiology possibly triggered by some environmental agent may precipitate hypocretin neuronal loss. Current treatment modalities alleviate the main symptoms of excessive daytime somnolence (EDS) and cataplexy and, to a lesser extent, reduce nocturnal sleep disruption, hypnagogic hallucinations, and sleep paralysis. Sodium oxybate (SXB), a sodium salt of γ hydroxybutyric acid, is a first-line agent for cataplexy and EDS and may help sleep disruption, hypnagogic hallucinations, and sleep paralysis. Various antidepressant medications including norepinephrine serotonin reuptake inhibitors, selective serotonin reuptake inhibitors, and tricyclic antidepressants are second-line agents for treating cataplexy. In addition to SXB, modafinil and armodafinil are first-line agents to treat EDS. Second-line agents for EDS are stimulants such as methylphenidate and extended-release amphetamines. Emerging therapies include non-hypocretin-based therapy, hypocretin-based treatments, and immunotherapy to prevent hypocretin neuronal death. Non-hypocretin-based novel treatments for narcolepsy include pitolisant (BF2.649, tiprolisant); JZP-110 (ADX-N05) for EDS in adults; JZP 13-005 for children; JZP-386, a deuterated sodium oxybate oral suspension; FT 218 an extended-release formulation of SXB; and JNJ-17216498, a new formulation of modafinil. Clinical trials are investigating efficacy and safety of SXB, modafinil, and armodafinil in children. γ-amino butyric acid (GABA) modulation with GABAA receptor agonists clarithromycin and flumazenil may help daytime somnolence. Other drugs investigated include GABAB agonists (baclofen), melanin-concentrating hormone antagonist, and thyrotropin-releasing hormone agonists. Hypocretin-based therapies include hypocretin peptide replacement administered either through an intracerebroventricular route or intranasal route. Hypocretin neuronal transplant and transforming stem cells into hypothalamic neurons are also discussed in this article. Immunotherapy to prevent hypocretin neuronal death is reviewed. Keywords: narcolepsy, cataplexy, emerging treatment, sodium oxybate, pitolisant, JZP-110, hypocretin peptide, immunotherapy
format	article
author	Abad VC Guilleminault C
author_facet	Abad VC Guilleminault C
author_sort	Abad VC
title	New developments in the management of narcolepsy
title_short	New developments in the management of narcolepsy
title_full	New developments in the management of narcolepsy
title_fullStr	New developments in the management of narcolepsy
title_full_unstemmed	New developments in the management of narcolepsy
title_sort	new developments in the management of narcolepsy
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/b15a6738adbc4be08828fb343f6c8a93
work_keys_str_mv	AT abadvc newdevelopmentsinthemanagementofnarcolepsy AT guilleminaultc newdevelopmentsinthemanagementofnarcolepsy
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New developments in the management of narcolepsy

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