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Myelin and White Matter Diseases

Myelin formation during postnatal brain development represents one of the most crucial steps in the establishment of mature white matter and of fully functional connections between neurons. Vittorio Gallo, PhD, and Li-Jin Chew, PhD, continue to study new cellular and molecular approaches that promote oligodendrocyte maturation, myelination, and white matter development. Dr. Chew continues to study signal transduction pathways that regulate oligodendrocyte development in cultured cells and in transgenic mice. The focus of these studies is on mechanisms that promote oligodendrocyte progenitor differentiation and developmental myelination under pathological conditions. Dr. Gallo continues to study oligodendrocyte progenitor cell migration during normal development and after white matter injury. A focus of Drs. Gallo and Chew’s studies is the function of Sox transcription factors in oligodendrocyte development and pathology. They identified downstream signaling pathways of Sox transcription factors that are involved in regulating specific phases of oligodendrocyte development. Additionally, Dr. Chew studies how inflammation impacts oligodendrocyte progenitor cell function in cellular maturation, myelin gene expression, and repair after demyelination injury. Recent studies have revealed roles for mitogen-activated protein kinase activity in cytokine control of white matter development and repair by oligodendrocyte progenitor cells. Current research in cultured cells and transgenic mouse models investigates the involvement of cytokineinduced kinase activation in the inhibition of proper oligodendrocyte progenitor cell maturation. By understanding the effects of chronic inflammation on the progenitor cells of developing white matter and in white matter lesions, it is hoped that therapeutic targets may be identified for strategies of pharmacological intervention.

White matter is brain tissue that carries information between the nerve cells in the brain and spinal cord. When white matter doesn’t develop the way it should, or is somehow damaged, the result can be mental retardation and developmental disabilities. Disorders associated with loss of white matter include leukodystrophies (an inherited form of white matter malfunction), acute demyelinating encephalomyelitis (ADEM), and cerebral palsy, which is the most common disorder associated with white matter malfunction.

Unfortunately, modern medicine has a very limited understanding of the causes of white matter diseases. Scientists at Children's National Health System are working to change that.

Investigators at Children's National study how white matter develops and grows, including the intricacies of these developmental processes in utero. Better understanding how typical white matter develops may help scientists learn how to stimulate re-growth of white matter after injury or deterioration. Developmental studies of white matter include study of the myelination and remyelination of white matter in murine (mouse) models. Investigators from the Center for Genetic Medicine Research through the White Matter Disease Program use advanced gene sequencing and protein analysis to develop new tools to diagnose and eventually treat white matter disorders, including:

  • Vanishing white matter disease
  • Alexander disease
  • Megalencephalic leukoencephalopathy with subcortical cysts
  • Oligodendrocyte precursor cells (OPC)
  • Hypomyelinating leukodystrophies (HML)
  • Unclassified or undiagnosed leukodystrophies

The White Matter Disease Program currently offers testing programs for vanishing white matter, unclassified white matter disease, and hypomyelinating leukodystrophies.
 

Faculty with interests in white matter diseases include:

 

 

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