Wolfram syndrome is caused by mutations in a single gene, but its effects on the body are far reaching – the disease leads to diabetes, hearing and vision loss, nerve cell damage that causes motor difficulties, and early death.
A relatively rare disease, Wolfram syndrome affects around one in 500,000 people.
Researchers at the Washington University School of Medicine in St Louis, the Joslin Diabetes Center in Boston and the Novartis Institutes for BioMedical Research have discovered a mechanism related to mutations in the WFS1 gene that will aid the understanding of Wolfram syndrome. Their findings may also be important in the treatment of other disorders.
The study by the group of American researchers has been published online in the journal Nature Cell Biology.
Insulin-secreting beta cells in the pancreas of patients with Wolfram syndrome are unable to produce enough cyclic adenosine monophosphate (cyclic AMP). As a result, the pancreas produces and secretes less insulin, and the cells eventually die.
Dr Fumihiko Urano, associate professor of medicine in Washington University's Division of Endocrinology, Metabolism and Lipid Research, explained the role, and importance, of AMP:
"I would compare cyclic AMP to money. You can’t just take something you make to the store and use it to buy food. First, you have to convert it into money. "Then, you use the money to buy food. In the body, external signals stimulate a cell to make cyclic AMP, and then the cyclic AMP, like money, can ‘buy’ insulin or whatever else may be needed."
The reason patients with Wolfram syndrome experience so many problems is due to mutations in the WFS1 gene which interfere with cyclic AMP production in beta cells in the pancreas. Through an understanding of this mutation and finding a way to control cyclic AMP production in specific tissues, sufferers of Wolfram syndrome could be cured.
The findings could also benefit those suffering from more common disorders such as type 2 diabetes.