Adeline Vanderver, MD, is the Director of the Myelin Disorders Clinic at Children’s National Health System. Dr. Vanderver is an international leader in the study of leukodystrophies, conditions that affect about one in 7,000 children.
Dr. Vanderver has been interested in solving the mysteries of inherited myelin disorders since she was a medical student. She was touched by families that had been trying for years to understand the medical condition their children were experiencing before receiving a diagnosis. Dr. Vanderver also is deeply involved in searching for genetic pathways that might explain how these conditions occur. Just as important, she says, is building community support for patients and their families.
The leukodystrophy research program has the following goals, all focused on the clinical and bench evaluation of subjects with leukodystrophy, or inherited disorders of the white matter of the brain:
1. Improved understanding of the mechanisms and natural history of Aicardi Goutières syndrome. AGS is caused by mutations in genes that encode nucleases and related proteins. It is hypothesized that accumulation of immunostimulatory DNA results in immune activation and destruction of neurologic tissue. We are the US site for a large international collaboration on AGS. We have run several patient clinics and have a biorepository. We are also currently exploring the role of autoantibodies in this disorder. Finally, we are starting a clinical trial in collaboration with the NIH (U01).
2. Improved understanding of the mechanisms of Vanishing White Matter disease. This disorder is caused by mutations in the cellular mechanisms for response to ER stress and initiation of protein translation (eIF2B or eukaryotic initiation factor 2B). We are exploring the effect of exaggerated endoplasmic reticulum stress on glial cells and propose a mechanism by which mutations in EIF2B would result in alteration in glial cell lineage development. This project uses existing primary glial cell cultures, a murine model and murine oligodendrocyte cell lines.
3. Improved understanding of the mechanisms of TUBB4A-related hypomyelination using glial cell models (Oli-neu) and neuronal models to assess the role of altered tubulin on trafficking and cellular integrity.
4. Undiagnosed Leukodystrophies Program. Over half of patients with inherited disorders of the white matter never achieve a specific diagnosis. We have a consortium, the Myelin Disorders Bioregistry Project, with over 900 enrolled patients and family members, enrolling more than 100 new participants each year. We propose to test the effectiveness of Next Generation Sequencing (NGS) as a diagnostic tool for the leukodystrophies.
Dr. Vanderver is an Associate Professor in the Departments of Neurology and Pediatrics, and Integrative Systems Biology at George Washington University Medical Center. She also works with the National Human Genome Research Institute at the National Institutes of Health.