Grant to renew annual clinic, advance understanding of rare disorder
From the WashU School of Medicine News…
Researchers at Washington University School of Medicine in St. Louis have received a five-year, $3 million grant to study Wolfram syndrome, a rare genetic disorder that causes neurologic problems, insulin-dependent diabetes and other serious conditions.
The new grant, from the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health (NIH), will help fund the continuation of a Wolfram clinic at Washington University for patients from around North America and the world. It also will allow Washington University investigators to strengthen their ties to researchers in the United Kingdom who have launched a clinical trial evaluating a potential treatment for the disorder.
Wolfram syndrome, which affects about one in every 500,000 people, is caused by mutations in a single gene. The disorder has been regarded mainly as a very severe form of type 1 diabetes, with hearing loss, vision loss and neurologic problems developing as the disease advances. Wolfram syndrome patients are at risk for a limited lifespan, often due to complications related to brain degeneration.
By following young children and adolescents for several years since the launch of the Wolfram clinic — conducted during the summer at Mallinckrodt Institute of Radiology (MIR) at the School of Medicine, and St. Louis Children’s Hospital — the researchers have learned that some of the neurologic problems associated with Wolfram syndrome begin very early and that some patients don’t develop diabetes until much later in the course of the illness.
“From our brain-imaging studies, it appears Wolfram syndrome fits into a category of disorders called hypo-myelinating developmental diseases,” said the study’s principal investigator, Tamara G. Hershey, PhD, the James S. McDonnell Professor of Cognitive Neuroscience and a professor of psychiatry and of radiology at the School of Medicine. “The pattern we see suggests that in certain key areas, the brain doesn’t make enough of a substance called myelin, which insulates axons that carry signals to and from nerve cells. This deficit in insulation may leave cells vulnerable to dysfunction and degeneration over time.”
Although insulin-dependent diabetes almost always is a component of Wolfram syndrome, Hershey said her research involving the Wolfram clinic suggests it may be easier to identify some of the earliest signs of the syndrome with neurologic testing.
“The neurologic symptoms appear early,” said Hershey, who also is chief of the Neuroimaging Laboratory at MIR. “Sensory functions — such as smell, balance and gait — all are abnormal at a really early stage of the game. In addition, using brain scans we can detect structural effects in the brain very early and follow them over time.”