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.

Prospective study of individuals at risk for spinocerebellar ataxia type 1, type 2, type 3 and type 6 (SCA1, SC2, SCA3, SCA6)

Project Coordinator

University Hospital Bonn Department of Neurology


Alexandra Dürr Hôpital de la Pitié-Salpêtrière ISERM U679 Department of Genetics Paris, France
Caterina Mariotti Fondazione IRCCS- Instituto Neurologico Carlo Besta Division of Biochemistry and Genetics Milano, Italy
Frédéric Rieux-Laucat ISERM Unit 768 Hôpital Necker Paris, France
Jörg Schulz University of Göttingen Department of Neurodegeneration and Restorative Research Göttingen, Germany
José Berciano University Hospital Marqués de Valdecilla Department of Neurology Santander, Spain
Lufger Schöls University of Tübingen Department of Neurology and Hertie-Institute for Clinical Brain Research Tübingen, Germany
Michael O. Glocker Proteome Center Rostock Institute of Immunology Rostock, Germany
Olaf Riess University of Tübingen Department of Medical Genetics Tübingen, Germany
Sophie Tezenas du Montcel University Pierre et Marie Curie EA 3974 Modeling Clinical Research Paris, France

Publications of the RISCA project

Major results of the project

The spinocerebellar ataxias (SCAs) are autosomal dominantly inherited progressive brain disorders that are characterized by motor coordination deficits, ataxia. SCAs are rare disorders affecting 3.0 to 4.2 : 100,000 inhabitants. Among the various genetic subtypes of the SCAs, SCA1, SCA2, SCA3 and SCA6 are the most common. As in all autosomal dominant disorders, 50% of the direct descendants of an SCA patient carry the mutation and will develop the disease, whereas the remaining 50% (non-carriers) will stay healthy. Since future therapies of SCAs will have to be initiated as early as possible, it is of critical importance to study the presymptomatic phase of SCAs, i.e those individuals who are still healthy, but carry the disease mutation. To study the presymptomatic phase of the common SCAs (SCA1, SCA2, SCA3, SCA6) we initiated RISCA, a longitudinal observational study of individuals at risk for one of these SCAs. RISCA enrolled 277 healthy adult individuals that descended from an SCA1, SCA2, SCA3 or SCA6 individual. Genetic testing was done anonymously. Evaluation included a number of tests of motor coordination, assessment of non-motor symptoms and brain imaging by magnetic resonance imaging (MRI).

Compared to non-carriers, (1) SCA1 and SCA2 mutations carriers had mild coordination deficits detected by clinical examination, (2) SCA3 carriers had eye movement abnormalities, (3) SCA1, SCA2 and SCA3 carriers performed worse in timed performance tests that assess motor coordination, and (4) SCA1 carriers had more non-ataxia symptoms. Coordination deficits were more pronounced, the shorter the calculated time to expected disease onset was. First deficits were detectable approximately 15 years before disease onset. In addition, cerebellar and brainstem volumes of SCA1 and SCA2 mutation carriers, as measured by magnetic resonance imaging (MRI) were reduced. There were no differences between carriers and noncarriers with respect to sleep, mood and health-related quality of life. The data of the RISCA study show that the presymptomatic stage of SCAs is characterized by mild coordination deficits and beginning tissue loss in the cerebellum and brainstem.

E-Rare 2012 - Created by Toussaint Biger