Vanishing White Matter Case Study

The use of stem cells for understanding and treating vanishing white matter
- A literature study
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Fia Cialdella (2168790), Prisca Leferink VUmc Amsterdam, The Netherlands
* commissioned by elective neuroscience study medicine bachelor year 3

1. ABSTRACT
Background: Vanishing White Matter disease (VWM) is one of the most frequently inherited childhood leukoencephalopathies. This disease clinically presents with cerebellar ataxia and spasticity, eventually leading to coma and death. Currently no treatment is available. Stem cells are cells that have the ability to renew themselves and can differentiate into each cell type. Since 2006 it is known

This progressive disease presents itself with cerebellar ataxia and spasticity. Rapid neurologic deterioration is triggered by minor stress conditions like fever or mild head trauma, and lead to coma and eventually death. A mutation in any of the five genes encoding the subunits of eukaryotic translation initiation factor eIF2B causes this clinical picture. The diagnosis of VWM is made by a MRI, which shows cystic degeneration of white matter shown, which is filled up by cerebrospinal fluid. At the end stage of VWM all brain white matter is replaced by cerebrospinal fluid (cf) (Mejaški-Bošnjak et al., 2009). Typical for the pathological picture is the affection of glial cells, including foamy oligodendrocytes and dysmorphic astrocytes There is no treatment available for VWM. The only advice that can be given is to avoid contact sports, vaccinate and swallowing antibiotics and antipyretics (Bugiani, Boor, Powers, Scheper, & van der Knaap, 2010) (Bugiani et al.,

developed a strategy to differentiate hIPSC’s into oligodendrocyte progenitor cells (OPCs). Because of the rejection of donor cells by allogeneic transplantations they would like to develop a method for autogenetic transplantation. To argue the myelination skill of these hIPSC OPC’s, they transplanted newborn homozygous shiverer immunodeficient mice with these cells into the corpus callosum. They used the same method that was used in the study of Windrem et. Al 2008. The mice were put down at the age of 3 or 4,5 months. Then their brains were assessed for donor cell spreading and compactness, nodal reconstitution and myelin production and the proportion of myelinated axons. They found the brains were more myelinated, had a higher density and more interlaminar tight junctions. They also discovered an anatomic reconstruction of the nodes of Ranvier. The animals that were transplanted lived significantly longer than the mice that were not transplanted. Until nine months after the transplant there were no tumors registered. These data suggest that there is a solution to this deadly myelin loss inherited disorder by IPSC’s which differentiate into OPCs. It should be noted that before the somatic cells will be transplanted the underlying genetic effect must be repaired in the donor cells before inducing them to OPSc’s. (Wang et al.,