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Narcolepsy Type 1 as an Autoimmune Disorder: Evidence, and Implications for Pharmacological Treatment

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Abstract

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.

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Authors and Affiliations

  1. Department of Neurology, Sleep-Wake Disorders Center, Gui-de-Chauliac Hospital, CHU Montpellier, 80 Avenue Augustin Fliche, 34295, Montpellier Cedex 5, France

    Lucie Barateau & Yves Dauvilliers

  2. National Reference Network for Narcolepsy, Montpellier, France

    Lucie Barateau & Yves Dauvilliers

  3. INSERM U1061, Montpellier, France

    Lucie Barateau & Yves Dauvilliers

  4. INSERM U1043-CNRS UMR 5282, Centre de Physiopathologie Toulouse-Purpan, University of Toulouse III, Toulouse, France

    Roland Liblau

  5. Center for Research in Neuroscience of Lyon, INSERM U1028, CNRS, UMR5292, University of Lyon 1, Lyon, France

    Christelle Peyron

Authors
  1. Lucie Barateau
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  2. Roland Liblau
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  3. Christelle Peyron
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  4. Yves Dauvilliers
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Corresponding author

Correspondence to Yves Dauvilliers.

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Funding

This was not an industry-supported study.

Conflicts of Interest

We declare no conflicts of interest related to this article. L. Barateau has received speaker’s fees from UCB Pharma and paid travel accommodation from Laidet Medical. Y. Dauvilliers has received funds for speaking, board engagements, and travel to conferences with UCB Pharma, Jazz and Bioprojet. R. Liblau and C. Peyron had no conflict of interest.

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Barateau, L., Liblau, R., Peyron, C. et al. Narcolepsy Type 1 as an Autoimmune Disorder: Evidence, and Implications for Pharmacological Treatment. CNS Drugs 31, 821–834 (2017). https://doi.org/10.1007/s40263-017-0464-6

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