Leukodystrophies (4H*, VWM*, MLD*, GLD*, and CD*)

“Leukodystrophies constitute a large group of different progressive brain disorders that lead to increasing handicap and death. Although individual disorders are rare to exceedingly rare (1: 50.000, 1:100.000), as a group the leukodystrophies affect ~1:2000 persons. Many have their onset early in life. Such diseases have a major impact on patients and families. Because leukodystrophies are genetically determined, often more than one child is affected within the same family. The development of new therapeutic strategies for these devastating disorders is hampered by a lack of mechanistic disease insight. Current research for leukodystrophies focuses on glial dysfunction. However, this model does not take into account the neuronal defects frequently observed in patients. A better understanding of the complex molecular and cellular interplay underlying the onset/progression of WM pathology and the recognition of the cellular pathology behind a leukodystrophy (or a group of them) have important therapeutic implications. In fact, defining the causative role of neuronal vs. glial cells to pathology will provide insights for the development of tailored therapies that may not (only) rely on cell-based remyelination strategies.”

 

Background

• Disease mechanisms are poorly elucidated in leukodystrophies
  • Therefore, to understand myelin phenotypes, we need to explore general and disease-specific pathogenic mechanisms involved in leukodystrophy types.
• Neuron-glia interdependent mechanisms regulate myelin integrity
  • Thus, to understand neuronal involvement in myelin defects, we need insight into neuron-glia interdependent mechanisms.

 

4H* Hypomyelination, Hypodontia, Hypogonadotropic, Hypogonadism Syndrome
VWM* Vanishing White Matter disease, or Childhood Ataxia with diffuse CNS Hypomyelination (CACH)
MLD* Metachromatic Leukodystrophy
GLD* Globoid Cell Leukodystrophy, or Krabbe Disease
CD* Canavan Disease