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.

The Netherlands
Targeting Rho-signalling, a new therapeutic avenue in fragile X syndrome

Project Coordinator

Center for Genomic Regulation Genes and Disease Program


Barbara Bardoni IMPC-CNRS, UMR6097 Valbonne, France
Gerard Ramakers University of Amsterdam Department of Developmental Psychology Amsterdam, The Netherlands
Giovanni Diana Istituto Superiore de Sanita Department of Therapeutic Research and Medicines Evaluation Rome, Italy
Oliver Stork Otto von Guericke University Magdeburg Insitute of Biology Department of Genetics & Molecular Neurobiology Magdeburg, Germany

Fragile X syndrome is caused by the loss of the Fragile X mental retardation protein (FMRP) encoded by the Fragile X mental retardation 1 (FMR1) gene. Moderate to severe mental retardation and autistic behavior are key features of Fragile X patients. Dendritic abnormalities that have been associated with mental retardation are found in Fragile X patients and Fmr1 knockout mice. The central role of Rho GTPases in controlling actin dynamics and structural plasticity indicates that pharmacological intervention at this level may be an effective strategy in Fragile X, where Rho GTPase signalling is altered. The project explores the possibility of cellular and behavioural rescue of Fragile X phenotypes using pharmacological Rho manipulation in Fmr1 knockout mouse, and addresses the mechanistic link between effective Rho-signalling drugs, their target proteins, and the structural and functional alterations that occur at the synapse in association with memory effects. The results should identify the Rho-signalling drugs that are most effective in Fragile X phenotypes, as well as their possible side-effects. The main objectives are to produce, deliver and analyze the pharmacological/neurobiological effects of Rho-signaling modulators in wild-type and Fmr1 knockout mice, the morphological and cellular correlates of effective Rho signalling treatments and the transcriptome analysis of effective Rho signalling drugs. These studies will be completed by analyzing the neuronal sublocalization of FMRP, its interacting-proteins and some of its target RNA upon Rho signalling drugs.


E-Rare 2012 - Created by Toussaint Biger