I often get the following question. “What is the link between Wolfram syndrome and type 1 diabetes?” My answer is “Endoplasmic reticulum dysfunction.”
Both Wolfram syndrome and type 1 diabetes are characterized by juvenile-onset diabetes. We need to note that some patients with Wolfram syndrome and type 1 diabetes develop diabetes in adulthood. Both in Wolfram syndrome and type 1 diabetes, beta cells in pancreas that produce insulin are destroyed. In type 1 diabetes, the etiology of beta cell death is autoimmunity. What is autoimmunity?
Our immune system protects us from invading organisms that can cause illness. In healthy states, our immune system does not attack our own cells. In type 1 diabetes, our immune system attacks our own pancreatic beta cells and destroys them. I call this “unintentional suicide.” What we don’t know is how autoimmunity is induced. Accumulating data in my lab and Dr. Emil Unanue’s lab at Washington University suggest that endoplasmic reticulum dysfunction creates “neoantigen” in our beta cells, leading to autoimmunity. Neoantigen means abnormal cell products that can be mistakenly recognized as invading organisms.
Because the root cause of Wolfram syndrome is endoplasmic reticulum dysfunction, it is possible that a novel drug or an intervention for Wolfram syndrome can be beneficial for patients with type 1 diabetes. This is still a theory. The theory does not help patients, the treatment based on the theory does.