PMID- 28940143
OWN - NLM
STAT- MEDLINE
DCOM- 20180607
LR  - 20200306
IS  - 1179-1934 (Electronic)
IS  - 1172-7047 (Linking)
VI  - 31
IP  - 10
DP  - 2017 Oct
TI  - Narcolepsy Type 1 as an Autoimmune Disorder: Evidence, and Implications for 
      Pharmacological Treatment.
PG  - 821-834
LID - 10.1007/s40263-017-0464-6 [doi]
AB  - Narcolepsy type 1 (NT1) is a rare sleep disorder caused by the very specific loss 
      of hypothalamic hypocretin (Hcrt)/orexin neurons. The exact underlying process 
      leading to this destruction is yet unknown, but indirect evidence strongly 
      supports an autoimmune origin. The association with immune-related genetic 
      factors, in particular the strongest association ever reported in a disease with 
      an allele of a human leukocyte antigen (HLA) gene, and with environmental factors 
      (i.e., the H1N1 influenza infection and vaccination during the pandemic in 2009) 
      are in favor of such a hypothesis. The loss of Hcrt neurons is irreversible, and 
      NT1 is currently an incurable and disabling condition. Patients are managed with 
      symptomatic medication, targeting the main symptoms (excessive daytime 
      sleepiness, cataplexy, disturbed nocturnal sleep), and they require a lifelong 
      treatment. Improved diagnostic tools, together with an increased understanding of 
      the pathogenesis of NT1, may lead to new therapeutic and even preventive 
      interventions. One future treatment could include Hcrt replacement, but this 
      neuropeptide does not cross the blood-brain barrier. However, Hcrt receptor 
      agonists may be promising candidates to treat NT1. Another option is immune-based 
      therapies, administered at disease onset, with already some initiatives to slow 
      down or stop the dysimmune process. Whether immune-based therapy could be 
      beneficial in NT1 remains, however, to be proven.
FAU - Barateau, Lucie
AU  - Barateau L
AD  - Department of Neurology, Sleep-Wake Disorders Center, Gui-de-Chauliac Hospital, 
      CHU Montpellier, 80 Avenue Augustin Fliche, 34295, Montpellier Cedex 5, France.
AD  - National Reference Network for Narcolepsy, Montpellier, France.
AD  - INSERM U1061, Montpellier, France.
FAU - Liblau, Roland
AU  - Liblau R
AD  - INSERM U1043-CNRS UMR 5282, Centre de Physiopathologie Toulouse-Purpan, 
      University of Toulouse III, Toulouse, France.
FAU - Peyron, Christelle
AU  - Peyron C
AD  - Center for Research in Neuroscience of Lyon, INSERM U1028, CNRS, UMR5292, 
      University of Lyon 1, Lyon, France.
FAU - Dauvilliers, Yves
AU  - Dauvilliers Y
AD  - Department of Neurology, Sleep-Wake Disorders Center, Gui-de-Chauliac Hospital, 
      CHU Montpellier, 80 Avenue Augustin Fliche, 34295, Montpellier Cedex 5, France. 
      y-dauvilliers@chu-montpellier.fr.
AD  - National Reference Network for Narcolepsy, Montpellier, France. 
      y-dauvilliers@chu-montpellier.fr.
AD  - INSERM U1061, Montpellier, France. y-dauvilliers@chu-montpellier.fr.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - New Zealand
TA  - CNS Drugs
JT  - CNS drugs
JID - 9431220
RN  - 0 (HLA-A Antigens)
RN  - Narcolepsy 1
SB  - IM
MH  - Animals
MH  - Autoimmune Diseases/*complications/*drug therapy/genetics
MH  - Causality
MH  - Disease Models, Animal
MH  - Environmental Exposure/adverse effects
MH  - HLA-A Antigens/genetics
MH  - Humans
MH  - Narcolepsy/*complications/*drug therapy/etiology/genetics
EDAT- 2017/09/25 06:00
MHDA- 2018/06/08 06:00
CRDT- 2017/09/24 06:00
PHST- 2017/09/25 06:00 [pubmed]
PHST- 2018/06/08 06:00 [medline]
PHST- 2017/09/24 06:00 [entrez]
AID - 10.1007/s40263-017-0464-6 [pii]
AID - 10.1007/s40263-017-0464-6 [doi]
PST - ppublish
SO  - CNS Drugs. 2017 Oct;31(10):821-834. doi: 10.1007/s40263-017-0464-6.