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
Patient-Derived Glial Precursor Cell Therapy for Vanishing White Matter Disease

Project Coordinator

VU University medical center
The Netherlands


Frank Edenhofer Medical University of Innsbruck Innsbruck, Austria
Gerald Schwank ETH Zurich, Institute of Molecular Health Sciences Zürich, Switzerland

Childhood white matter (WM) disorders (CWMDs) constitute a large group of rare disorders. The “leukodystrophies” are the genetically determined progressive CWMDs. We focus on the relatively prevalent leukodystrophy “Vanishing White Matter” (VWM), caused by recessive mutations in any of the 5 genes encoding translation initiation factor eIF2B (EIF2B1-5). VWM patients show increasing handicap and early death. Neuropathologic findings indicate a selective disruption of glia in the brain WM. There is no treatment. Currently cell replacement therapies have realistic therapeutic prospects. Experimental studies in animals have shown that cell transplants can improve brain function. The first FDA-approved clinical trials for CWMDs have shown acceptable safety outcome after 1 year. Our aim is to investigate the prospects of cell replacement therapies for patients with VWM. We will generate induced neural stem cells (iNSCs) from VWM patient fibroblasts. To correct the EIF2B gene defect, iNSCs will be genetically repaired by the CRISPR/Cas9 genome editing technology. Subsequently, genetically-corrected iNSCs will be differentiated into glial precursor cells. Efficacy and safety of transplantation of the iNSC-derived cells will be tested in VWM mouse models. We recently developed 2 VWM mouse models, which show progressive neurological dysfunction and WM abnormalities closely resembling human VWM. If a cell therapy approach will prove beneficial in VWM mice, this will become an important new strategy in treating numerous different WMDs associated with severe handicap in patients.

E-Rare 2012 - Created by Toussaint Biger