Alexander disease is a very rare brain disease. People with Alexander disease experience damage to the white matter in their brains, and they lose a lot of brain tissue. It can be diagnosed when a person is very young, even before they turn 2 years old, but sometimes it is not diagnosed until later in childhood or even adulthood. The symptoms of Alexander disease include problems with mental development, seizures, and muscle stiffness, and it ultimately leads to death. There have been about 500 cases of Alexander disease reported around the world. Unfortunately, there is currently no cure for this disease.

The disease is caused by mutations in the gene glial fibrillary acidic protein (GFAP), which codes for an astrocyte‐specific cytoskeletal protein. Astrocytes are essential for healthy brain functioning because they control many neuronal activities and homeostatic mechanisms of the brain. However, scientists still do not fully understand how this mutant GFAP protein in astrocytes causes Alexander disease.

In this project, we will closely collaborate between two teams to investigate Alexander patient‐derived human stem cell models at the ultrastructural level. We will generate miniature brain‐like structures called organoids from patient‐derived stem cells, and apply novel cell culture protocols to include white matter‐like structures. By analysing the cells in these organoids at the ultrastructural level, we will gain more knowledge on how GFAP mutations can lead to astrocyte and white matter pathology in the disease. This knowledge is essential to find new ways to treat Alexander disease.