News

E-Rare "European Research Projects on Rare Diseases' project awarded.

Mark Verheijen & Gert Scheper, Huib Mansvelder and Marjo van der Knaap acquire 450 k€ grant in collaboration with Raúl Estévez from University of Barcelona to study childhood white matter diseases.

Cultured astrocyten infected with scrambled virus. GFP is green, MLC is red.


Neuroscience Campus collaborating team of Mark Verheyen, Gert Scheper, Huibert Mansvelder and Marjo van der Knaap aims at gaining insight into the disease mechanisms of MLC in order to find openings for treatment.


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. The macrocephaly and white matter abnormality, as visualized by MRI, develop during the first year of life, the period of most active myelin deposition in the human brain. MLC1 is the first gene demonstrated to be involved in this disease. It encodes a transmembrane protein of unknown function, which has a homology to ion channels, but ion channel function has so far not been confirmed. The MLC1 protein is enriched in neurons at early stages and in astrocytes at later stages of development. It is expressed mainly in astroglial processes and axonal tracts. MLC is one of the very few known genetic diseases with astroglial dysfunction. MLC1 mutations reduce MLC1 protein levels. 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.

                                                                                                                 CNS myelin

This Neuroscience Campus project will lead to increased insights into the functions of the protein MLC1, from molecular interactions to its physiological role in water homeostasis in the brain. The collaborators expect that, based on the outcome of the research proposed, that they will be able to design screening studies aimed at identifying molecules that could be used for therapy. The effects of such therapies can then be further tested in recently generated animal models.



Mixed culture of neurons (red) and astrocyten (green)