s ingediend voor het Amsterdam Kindersymposium 2013 35 The influence of Vanishing White Matter mutations on oligodendrocyte differentiation S. Dooves (1,2), J.A. van der Kreeke (1,2), P. Leferink (1,2), J.G. Jacobs (1,2), M.S. van der Knaap (1), V.M. Heine (1,2) (1) Center for Children with White Matter Disorders, Pediatrics, VU University Medical Center, Amsterdam (2) Stem Cell Laboratory, VU University/VU University Medical Center, Amsterdam INTRODUCTION Vanishing White Matter disease (VWM) is an autosomal recessive leukoencephalopathy caused by mutations in genes encoding the eukaryotic translation initiation factor 2B (eIF2B). Children are mainly aff ected, who suff er from progressive neurological symptoms as ataxia and die at young age. Previous research indicates that the macroglial cells of the brain (astrocytes and oligodendrocytes) in VWM show a defect in maturation. Currently there is no treatment available. METHODS In order to gain more knowledge about the disease pathology we tested the diff erentiation capability of stem cells derived from VWM mice in culture. Furthermore, a co-culture system is used to test the infl uence of VWM mutated astrocytes on the diff erentiation of WT oligodendrocyte precursor cells (OPCs). RESULTS The fi rst results show that VWM mutated astrocytes have a negative eff ect on the maturation of oligodendrocytes. CONCLUSION Astrocytes with a VWM mutation have a negative infl uence on OPC maturation. Further studies will show if it is possible to rescue this maturation defect. The results will give us more information about the disease mechanisms of VWM and will help in the development of a cell replacement therapy for VWM.