Eugene Devic European Network

Devic`s neuromyelitis optica (DNMO) is a rare demyelinating and inflammatory disease of the central nervous system with recurrent attacks of optic neuritis, myelitis or both, characterized by a high rate of morbidity and mortality when not diagnosed promptly and treated appropriately. DNMO is now considered to be an auto-immune disease, mediated by a specific serum autoantibody directed against AQP4. However, DNMO patients are still often misdiagnosed for multiple sclerosis. Moreover, there are still many unresolved issues and unmet needs in DNMO: unknown ethiology and pathophysiology; clinical spectrum of the disease; biomarkers; prognostic markers; standardization of treatments; medicoeconomic cost. Thus, EDEN aims at: Set-up a European database for DNMO to describe the demographic, clinical, radiological and biological features and the clinical course with and without specific treatments. Create standardised biobanks for DNMO for biomarkers and pathophysiology studies Set up European gold standard for AQP4 Ab detection, develop prognostic tests and research for new biomarkers Develop and validate models for DNMO Propose standardised therapeutic procedures to improve management of patients Disseminate procedures to improve communication to patients and clinicians EDEN, through a systematic longitudinal follow-up collection of data for multimodal assessments of patients will contribute to a comprehensive and homogeneous description of DNMO, standardise medical practice and bring new insights on physiopathology, paving the way to future clinical trials.

The Eugène Devic European Network (EDEN) project aimed to create a European research network focused on the diagnosis, pathogenesis and therapy of neuromyelitis optica. Neuromyelitis optica (NMO) is a rare chronic inflammatory disease of the central nervous system, leading to demyelination and neurodegeneration mainly affecting the spinal cord and optic nerves. Recently a specific auto-antibody has been discovered, which reacts with the astrocytic water channel aquaporin 4, which is highly specific for the disease. Aim of this project was to define the clinical spectrum of the disease, to identify the most reliable laboratory test system for the identification of aquaporin 4 antibodies, to shed light on the pathophysiological mechanisms of the disease and to validate the effectiveness of different anti-inflammatory and immunomodulatory treatments. The consortium contained groups from France (coordinator), from Austria, Germany, Great Britain and Turkey. The subproject, funded by the Austrian Science Foundation, was mainly devoted to improve the antibody test systems and to elucidate disease mechanisms. It was performed in close cooperation between the Center for Brain Research of the Medical University of Vienna and the Department of Neurology of the Medical University of Innsbruck. In the course of the project we were able to define that cell based antibody assays, as they had been established in the Innsbruck group, are currently the most sensitive and specific diagnostic tests. Based on this test system it was then possible to define the clinical spectrum of the disease, which turned out much broader than originally expected. Regarding pathogenesis, we found that the respective antibodies are essential to induce the lesions within the brain and spinal cord, but that in addition T-cell mediated immune reactions are important to start the disease process. We also found that NMO patients, who do not have the respective aquaporin 4 autoantibodies may have other autoantibodies directed against myelin oligodendrocyte glycoprotein and we have established the respective diagnostic test systems. The validity of the respective studies and test systems have been validated in the course of the project in cooperation with the international partners.