Funding transnational collaborative research through joint transnational calls is one of the major objectives of E-Rare. This is the most important and effective joint activity to enhance the cooperation between European scientists working on rare diseases and thus reducing the fragmentation of research in this field. E-Rare launches calls on a yearly basis. The topic and eligibility criteria are specified every year and therefore may vary from one call to the other.

Deciphering the immunopathogenesis of type 1 nacolepsy with omics

Project Coordinator



Yves DAUVILLIERS INSERM Montpellier, France
Klaus DORNMAIR Biomedical Center and University Hospital Planegg-Martinsried, Germany
Mehdi TAFTI University of Lausanne Lausanne, Switzerland

"Narcolepsy-cataplexy (NT1) is a rare, chronic, and disabling neurological disease characterized by excessive daytime sleepiness and sudden loss of muscle tone. It is due to the selective loss of neurons producing the orexin neuropeptide in the hypothalamus.The notion that NT1 is an autoimmune disorder is supported by its strong association with the HLA-DQB1*06:02 allele and by the striking association between vaccination against the 2009 pandemic H1N1 influenza virus and occurrence of NT1. Moreover, our recent data in mice and men strongly supports the involvement of T cells in the pathogenesis of NT1. 

The major goals of this proposal are to elucidate the immune mechanisms triggering NT1, to detect and isolate clonally expanded T cells in NT1 and use them to identify the potential autoantigen(s) and autoreactive T cells responsible for the destruction of orexin-producing neurons using integrated transcriptomic and proteomic approaches making use of T cells from patients as well as iPSC-dervived neurons.To this goal we have already collected probably the largest European biobank of cryopreserved PBMC, serum, and CSF from patients with NT1 and from patients with other sleep disorders, as well as PBMC from age-, sex-, and HLA-DQB1*06:02-matched healthy controls.In depth molecular information as those generated in the frame of this collaborative project will pave the way to such targeted trials. In addition, identification of the target autoantigen(s) will be a major breakthrough in the understanding of NT1 pathogenesis, with implications extending beyond this disease."


E-Rare 2012 - Created by Toussaint Biger