TY - JOUR

T1 - Emerging therapeutic targets for narcolepsy

AU - Vringer, Marieke

AU - Kornum, Birgitte Rahbek

PY - 2023

Y1 - 2023

N2 - Introduction Narcolepsy type 1 (NT1) and type 2 (NT2) are chronic sleep disorders primarily characterized by excessive daytime sleepiness (EDS), disturbed sleep-wake regulation, and reduced quality of life. The precise disease mechanism is unclear, but it is certain that in NT1 the hypocretin/orexin (Hcrt) system is affected. Current treatment options are symptomatic – they improve EDS and/or reduce cataplexy. Complete symptom control is relatively rare – particularly problematic is residual daytime sleepiness. Areas covered This review discusses various emerging treatment targets for narcolepsy. The focus is on the Hcrt receptors but included are also wake-promoting pathways, and sleep-stabilization through GABAergic mechanisms. Additionally, we discuss the potential of targeting the likely autoimmune basis of narcolepsy. PubMed and ClinicalTrials.gov was searched through June 2021 for relevant information. Expert opinion Targeting Hcrt receptors has the potential to alleviate narcolepsy symptoms. Results from ongoing drug development programs are promising, but care needs to be taken when evaluating potential side effects. It is still largely unknown what roles Hcrt receptors play in the periphery and how these might be affected by treatment. Immunotherapies could potentially target the core pathophysiology of narcolepsy, but more work is needed to identify the best therapeutic target for this approach.

AB - Introduction Narcolepsy type 1 (NT1) and type 2 (NT2) are chronic sleep disorders primarily characterized by excessive daytime sleepiness (EDS), disturbed sleep-wake regulation, and reduced quality of life. The precise disease mechanism is unclear, but it is certain that in NT1 the hypocretin/orexin (Hcrt) system is affected. Current treatment options are symptomatic – they improve EDS and/or reduce cataplexy. Complete symptom control is relatively rare – particularly problematic is residual daytime sleepiness. Areas covered This review discusses various emerging treatment targets for narcolepsy. The focus is on the Hcrt receptors but included are also wake-promoting pathways, and sleep-stabilization through GABAergic mechanisms. Additionally, we discuss the potential of targeting the likely autoimmune basis of narcolepsy. PubMed and ClinicalTrials.gov was searched through June 2021 for relevant information. Expert opinion Targeting Hcrt receptors has the potential to alleviate narcolepsy symptoms. Results from ongoing drug development programs are promising, but care needs to be taken when evaluating potential side effects. It is still largely unknown what roles Hcrt receptors play in the periphery and how these might be affected by treatment. Immunotherapies could potentially target the core pathophysiology of narcolepsy, but more work is needed to identify the best therapeutic target for this approach.

KW - Hypocretin

KW - orexin

KW - hypocretin receptor agonists

KW - immunotherapies

KW - narcolepsy

KW - stimulants

KW - OREXIN RECEPTOR ANTAGONISTS

KW - ONSET CHILDHOOD NARCOLEPSY

KW - INTRAVENOUS IMMUNOGLOBULIN

KW - HYPOCRETIN OREXIN

KW - OREXIN/HYPOCRETIN NEURONS

KW - DOUBLE-BLIND

KW - A HYPOCRETIN-1

KW - NON-REM

KW - SLEEP

KW - CATAPLEXY

U2 - 10.1080/14728222.2021.1969361

DO - 10.1080/14728222.2021.1969361

M3 - Review

C2 - 34402358

VL - 25

SP - 559

EP - 572

JO - Expert Opinion on Therapeutic Targets

JF - Expert Opinion on Therapeutic Targets

SN - 1472-8222

IS - 7

ER -