4H syndrome, an inherited brain white matter disorder (leukodystrophy), leads to considerable clinical handicap, ranging from mild to severe. Most patients deteriorate over time. There is no treatment yet, and we do not understand what goes wrong in the brain. There are no good animal models for this disease, hampering research. We think that besides white matter and myelin, also the nerve cells (neurons, also called grey matter) and their processes (axons) are damaged from early disease stages on. In our project, we want to explore this grey matter involvement with an innovative approach.

We are able to make white and grey matter cells from 4H patient and control fibroblasts. Earlier studies showed that 4H patient cells show affected expression of genes involved in nerve cell development. As nerve cells provide signals to white matter cells and myelination, neuronal defects could underlie abnormalities found in grey and white matter areas in 4H patient brains. We want to study co-cultures of both grey and white matter cells derived from patient cells to know how they influence each other. In the future, this might be a good model for drug screening to treat 4H.

Project financed by ELA up to: 99 565 €