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.

Spain
The Netherlands
MLC-Team
Megalencephalic leukoencephalopathy with subcortical cysts: from molecular basis to search for therapy

Project Coordinator

IDIBELL Ciencias Fisiologiques II
L'Hospitalet de Llobregat
Spain

Partners

Huibert Mansvelder VU University Medical Center Integrative Neurophysiology Amsterdam, The Netherlands
Marjo S. van der Knaap VU University Medical Center Child Neurology Amsterdam, The Netherlands
Mark Verheijen Center for Neurogenomics and Cognitive Research Molecular and Cellular Neurobiology Amsterdam, The Netherlands

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare, genetic brain disease, clinically characterized by early-onset macrocephaly and after a few years slow deterioration of motor functions, epilepsy and mental decline. In MLC, the cerebral myelin is vacuolated, causing white matter swelling. MLC1 is the first gene demonstrated to be involved in this disease. It encodes a transmembrane protein of unknown function. The MLC1 protein is enriched in neurons and in astrocytes. MLC is one of the very few known genetic diseases with astroglial dysfunction. At present, there is no insight into the pathophysiology of MLC; specific therapy is not available. MLC1 mutations are found in 75% of the MLC patients. Genetic linkage studies have demonstrated that there are other, as yet unidentified, disease genes. The planned experiments aim at gaining insight into the disease mechanisms of MLC in order to find openings for treatment. They comprise the characterization of MLC mouse models and the generation and characterization of a zebra fish MLC model. In addition, they include the analysis of cells with decreased MLC1 expression and the characterization of the recently identified MLC1 interactome. Potentially, other MLC disease genes will be found among the related genes. Our multidisciplinary approach will lead to increased insights into the functions of MLC1. We expect that, based on the outcome of the research proposed, we will be able to design screening studies aimed at identifying molecules that could be used for therapy.

E-Rare 2012 - Created by Toussaint Biger