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Interview with Dr. Rosa Peraita-Adrados for the 4th European Narcolepsy Day 2013

18/03/2013 ● Lecturas 42.502

Dra. Rosa Peraita-Adrados Clinical neurophysiologist and Head of the Sleep Disorders and Epilepsy Unit, Clinical Neurophysiology Service, Hospital General Universitario Gregorio Marañón, Madrid. Co-founder, with Prof. Antonio Vela-Bueno, of the Asociación Ibérica de Patologí
Question. Could you tell us how you became interested in narcolepsy?
Answer. My first encounter with narcolepsy patients was in the 1970s, as a research fellow at Dr. William Dement's Sleep Disorders Clinic & Laboratory at Stanford University. In July 1975, I participated in the First International Symposium on Narcolepsy held in La Grande Motte (France). Since that time, my contact with Professor M. Billiard has been essential. In the 1990s, he established the first European team study of the genetics of narcolepsy, and invited me to participate. At my hospital I then created a comprehensive database of narcoleptic patients from different parts of the country, and I began my collaboration with the immunologist José L. Vicario and the geneticist Mehdi Tafti, of the University of Lausanne.

In 1998, Javier Espinar and I organized a meeting of narcolepsy patients from all over Europe for the 14th ESRS Congress in Madrid. One year later the Spanish Narcolepsy Association (AEN) was founded in Madrid. In 2008, I joined the European Narcolepsy Network (EU-NN) chaired by Gert Jan Lammers, and was elected by the board to organize this upcoming 4th European Narcolepsy Day in Madrid, on March 16th and 17th.

Q. What have been the EU-NN's main goals over the past 5 years?
A. The network has been fundamental both for knowledge exchange among specialists and for the development of projects. Some of these projects have produced important publications in the field. For example, as a result of this network, my hospital collaborated in studies such as Lammers GJ et al. Sodium oxybate is an effective and safe treatment for narcolepsy. Sleep Med 2010; 11: 105-6; Hor H et al. Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy. Nat Genet 2010; 420: 786-9; Maurovich Horvat E et al. Narcolepsy and pregnancy: a retrospective European evaluation of 249 pregnancies (JSR, in press); Luca G et al. Clinical, Polysomnographic, and Genome-Wide Association Analyses of Narcolepsy with Cataplexy: A European Narcolepsy Network Study (JSR, in press).

Q. What, in your opinion, is the most significant contribution to the study of narcolepsy made by the Sleep Unit that you head?
A. Without a doubt, our most significant contribution has been the study of the Madrid family with 12 cases of narcolepsy-cataplexy. To identify a causative mutation in familial narcolepsy, we performed linkage analysis in the largest family study ever reported, and sequenced coding regions of the genome (exome sequencing) of three members affected with narcolepsy and cataplexy. We successfully mapped a candidate locus on chromosomal region 6p22.1 by linkage analysis. Exome sequencing identified a missense mutation in the second exon of myelin oligodendrocyte glycoprotein (MOG) within the linkage region. A c.398C>G mutation was present in all affected family members but absent in unaffected members and 775 unrelated control subjects. Transient expression of mutant MOG in mouse oligodendrocytes showed abnormal subcellular localization, suggesting an altered function of the mutant MOG. MOG has recently been linked to various neuropsychiatric disorders and is considered a key autoantigen in multiple sclerosis and in its animal model, experimental autoimmune encephalitis. Our finding of a pathogenic MOG mutation highlights a major role for myelin and oligodendrocytes in narcolepsy and further emphasizes glial involvement in neurodegeneration and neurobehavioral disorders (Hor H, Bartesaghi L, Kutalik Z, Vicário JL, de Andrés C, Pfister C et al. A missense mutation in myelin oligodendrocyte glycoprotein as a cause of familial narcolepsy with cataplexy. Am J Hum Genet 2011; 89: 474-9.)

Q. What topics will be discussed during the 4th European Narcolepsy Day in Madrid?
A. We will be discussing current issues that have been the subject of much study in the last few years, including physiopathology, genetics, and metabolic aspects of the disease. Infant narcolepsy is another important area that has enabled us to establish the semiological aspects of cataplexy. Other significant topics include differential diagnostics and the relationship with other hypersomnias in the central nervous system; pharmacological and non-pharmacological treatments; the socio-economic costs of the disease, etc. We will also present the EU-NN's database, both retrospective and prospective, which is the result of a joint effort of many collaborators and is contributing to fundamental publications such as those I mentioned before. The Day of the Patient is another feature of the meeting. Patients will meet with representatives from many European countries to establish a European Federation of Narcoleptics, which will bring many benefits to those suffering this disease, in terms of therapies and work issues. A central focus of this day will also be schooling and learning for narcoleptic children, improving their interaction in social and familial environments, and enhancing the dissemination of information and understanding of the disease.

Q. What contributions will your group make to this scientific meeting?
A. I have been working with colleagues from the Clinical Hospital of San Carlos, Francisco-Javier Martinez-Orozco and Isabel Villalibre, to study the relationship between narcolepsy-cataplexy and other neurological and non-neurological autoimmune HLA class II–associated diseases. Studying an ample number of patients, we have come to some interesting, although preliminary, conclusions that we want to propose for a European-wide study. Along with Rafael Del Rio from the La Paz Hospital, we have studied environmental stressor factors, and infectious diseases in connection with early manifestations of the disease. Epidemiological studies of narcolepsy are few and we believe that some of our findings will be useful in guiding future research in this area.
Prof. Juan-Vicente Sanchez-Andrés
Director asociado de Revista de Neurología
Departamento médico, Viguera eds.
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