The project

Genetic brain white matter disorders, also called leukodystrophies, lead to considerable clinical handicap, ranging from mild to severe. Patients are most often children and die early in life. As yet, the majority of leukodystrophies lack an effective treatment. While all leukodystrophies share major pathological traits (i.e. white matter disruption), our understanding of the cascade of events leading from the genetic defect to this detrimental outcome is still poor. Recent evidences suggest 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.

NG4Leuko project aims at exploring this grey matter involvement in different types of leukodystrophies with an innovative approach. Modern –OMICS and high-resolution imaging will be combined with advanced 2D and 3D induced pluripotent stem cell (iPSC)-based cellular models. We want to study patient grey and white matter cells using different model systems, from reductive in vitro cultures up to complex in vivo microenvironments, to know how they influence each other, and whether different patients present with common defects. In the future, this might be a good approach to study for drug screening for leukodystrophies. To reach this goal, the project will combine the expertise of

• recognized European research teams working in the field of white matter diseases
• and leukodystrophy patients and families associations devoted to leukodystrophies.