Why Wolfram Syndrome Matters

Increasing evidence indicates that ER stress, and ultimately cell death, plays a significant role in common forms of diabetes as well as neurodegenerative diseases including ​Alzheimer’s disease, Parkinson’s disease, and ALS.

Wolfram Syndrome

Absence of a single gene
ER dysfunction
Beta cell death Neurodegeneration

Common Diseases

Multiple genetic factors
  • ER dysfunction
  • Oxidative stress
  • Impaired cell signaling
  • Multiple other causes
Beta cell death Neurodegeneration
Environmental factors

WS offers an exquisite example of the role of endoplasmic reticulum (ER) stress in disease. WS is more likely to reveal the mechanisms of ER stress-mediated cell death than other common conditions in which multiple factors typically interact to produce the disease. Thus WS represents an ideal model to help determine the underlying causes of cell death in ER stress-mediated diseases.

Originally thought to be a 1/500,000 disease, there is new evidence that mutations of WFS1 occur with far greater frequency in certain populations. This results in increased incidence and prevalence of wolfram-like syndrome, presenting as Type 1 diabetes or optic nerve atrophy. The study of Wolfram syndrome may lead to a breakthrough for treatments of not only Wolfram syndrome, but also more common diseases such as type 1 diabetes, type 2 diabetes, and neurodegenerative diseases.