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Reply to 'Promotion of sleep by targeting the orexin system in rats, dogs and humans'

Nature Medicine volume 13, pages 525–526 (2007)Cite this article

To the editor:

Loss-of-function mutations in the orexin-2 receptor gene cause narcolepsy with cataplexy in dobermans and labradors1. Lack of orexin-A and orexin-B in mice results in a narcolepsy-like phenotype with behavioral arrests reminiscent of cataplexy2. Orexin deficiency in humans is the most specific biomarker of narcolepsy with cataplexy3. Orexin deficiency in humans is linked to cataplexy almost 100% of the time, whereas its association with narcolepsy with excessive sleepiness but no cataplexy is less strong (30–50%)4. On the basis of these and other data, there is strong evidence indicating that loss-of-function mutations of orexin or its receptors underlie excessive sleepiness and, more specifically, cataplexy in humans and animal models of narcolepsy. So, orally active compounds that would replace endogenous orexins are pharmacological targets of great therapeutic value in narcolepsy. On the other hand, an orexin receptor antagonist could be expected to induce narcolepsy and/or cataplexy, and the development of such a drug to treat insomnia should be evaluated with extreme care, especially with regard to its long-term effects.

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References

  1. Lin, L. et al. Cell 98, 365–376 (1999).

    Article  CAS  Google Scholar 

  2. Chemelli, R.M. et al. Cell 98, 437–451 (1999).

    Article  CAS  Google Scholar 

  3. Mignot, E. et al. Arch. Neurol. 59, 1553–1562 (2002).

    Article  Google Scholar 

  4. Dauvilliers, Y. et al. Lancet 369, 499–511 (2007).

    Article  Google Scholar 

  5. Brisbare-Roch C. et al. Nat. Med. 13, 150–155 (2007).

    Article  CAS  Google Scholar 

  6. Kanbayashi T. et al. Neuroreport 12, 1881–1886 (1996).

    Article  Google Scholar 

  7. Nishino S. et al. Sleep 17, S84–S92 (1994).

    Article  CAS  Google Scholar 

Download references

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  1. University of Lausanne, Center for Integrative Genomics (CIG), Génopode Building, Lausanne, 1015, Switzerland

    Mehdi Tafti

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  1. Mehdi Tafti
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Tafti, M. Reply to 'Promotion of sleep by targeting the orexin system in rats, dogs and humans'. Nat Med 13, 525–526 (2007). https://doi.org/10.1038/nm0507-525

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