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Narcolepsy, scientists unmask the culprit of an enigmatic disease

21-Sep-2018

Patients with a rare disease, called narcolepsy, suffer of excessive daytime sleepiness and cataplexy (brief episodes of loss of muscle tone triggered by emotions). A study published in Nature reports, for the first time, the existence in patients with narcolepsy of autoreactive T lymphocytes (cells of the immune system) that recognize hypocretin and can mediate an immune response leading to loss of hypocretin-producing neurons. This study identifies the culprit of this enigmatic disease and has major implications for its diagnosis and therapy.

Patients with a rare disease, called narcolepsy, suffer of excessive daytime sleepiness and cataplexy (brief episodes of loss of muscle tone triggered by emotions). The disease, first described in 1877, depends on genetic and environmental factors and is caused by the loss in the brain of some neurons that produce a neurotransmitter called hypocretin, but the underlying mechanism remained mysterious. A study published in the renowned scientific journal Nature reports, for the first time, the existence in patients with narcolepsy of autoreactive T lymphocytes (cells of the immune system) that recognize hypocretin and can mediate an immune response leading to loss of hypocretin-producing neurons. This study identifies the culprit of this enigmatic disease and has major implications for its diagnosis and therapy.

The study is the result of a close collaboration between basic and clinical scientists and was jointly coordinated by Prof. Federica Sallusto at the Institute for Research in Biomedicine in Bellinzona (IRB, affiliated to USI Università della Svizzera italiana) and at ETH Zurich, and Prof. Claudio Bassetti at the University Sleep-Wake-Epilepsy-Center Bern of the Department of Neurology at the University Hospital (Inselspital) in Bern. The study also involved the Neurocenter of Southern Switzerland of the Ente Ospedaliero Cantonale, the Center for Sleep Research and Sleep Medicine of the Clinic Barmelweid, the Department of Physiology at the University of Lausanne, the Institute of Experimental Immunology at the University of Zurich, and the Institute of Immunology at the University Witten/Herdecke in Germany. The work was supported by the Swiss National Science Foundation, the European Research Council (ERC) and the Helmut Horten Foundation.

According to Prof. Federica Sallusto: «Using new sensitive methods we have been able to identify T lymphocytes reactive against hypocretin as the culprit of this disease. These autoreactive T lymphocytes can cause inflammation leading to neuronal damage or even kill hypocretin-producing neurons. By blocking them at early stages, it may be possible to limit neuronal loss and prevent progression of the disease.»

According to Prof. Claudio L.A. Bassetti: «This publication will increase the awareness about narcolepsy, which remains poorly known in the general population and often is not, or belatedly, diagnosed by physicians. This study will also open new opportunities for an early diagnosis and novel treatment approaches of this disabling disease.»

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