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.

Lipid metabolism in the pathogenesis of hereditary spastic paraplegia: genes, biomarkers, and models for therapy

Project Coordinator

University of Cologne


Maria Teresa Bassi IRCCS E. MEDEA Scientific Institute Bosisio Parini (Lecco), Italy
Rebecca Schüle Hertie Institute for Clinical Brain Research and Center for Neurology Tübingen, Germany
Giovanni Stevanin Centre de Recherche de l’Institut du Cerveau et de la Moelle épinière Paris, France

Hereditary spastic paraplegia (HSP) defines a genetically heterogeneous group of disorders characterized by weakness and spasticity of the lower limbs, owing to retrograde degeneration of corticospinal axons. Recently, both genetic and functional studies, largely contributed by research from members of this consortium, have revealed a pathogenic link of HSP with lipid metabolism, pointing to defects in cholesterol (SPG5), fatty acid (SPG49), phospholipid (SPG28, SPG39, SPG54), sphingolipid (SPG26, SPG35, SPG46) metabolism, and lipid droplet turnover (SPG3, SPG4, SPG17, SPG20, SPG31). These data open the way to the identification of novel biomarkers for this pathology, and suggest that therapeutic approaches aiming at restoring normal lipid profiles may prove beneficial in HSP. Lipid composition of biological membranes affects several physiological processes of crucial relevance in neurons, such as endo- and exocytosis, trafficking, and dynamics of organelles. Moreover, lipid molecules may act as direct signalling effectors. Our proposal brings together four groups with complementary expertise with the object to: 1) Establish frequency, natural history, and genotype/phenotype correlations of HSP forms linked to lipid metabolism; 2) Perform lipidomic studies on cell lines and tissues derived from HSP patients and animal models to identify novel biomarkers; 3) Assess cellular consequences of changes in lipid composition and lipid droplets in these forms of HSP; 4) Develop mouse and Drosophila models for a subset of these genes to be used for future preclinical trials.

E-Rare 2012 - Created by Toussaint Biger