Wolfram Syndrome and Endoplasmic Reticulum Disorders
Wolfram syndrome is a rare autosomal recessive genetic disorder with clinical signs apparent in early childhood. This condition is characterized by juvenile-onset diabetes, optic nerve atrophy, deafness, diabetes insipidus and neurodegeneration, and it may result in death in middle adulthood.
Accumulating evidence in my laboratory strongly suggests that endoplasmic reticulum (ER) dysfunction is a critical pathogenic component of Wolfram syndrome. However, a complete understanding of the pathways and biomarkers involved in the disease process is still lacking. As a result, despite the underlying importance of ER dysfunction in Wolfram syndrome, there are currently no therapies that target the ER.
The goal of our laboratory is to reveal the molecular mechanisms of Wolfram syndrome and develop patient-based therapeutics for this complex disorder using genetic information from each patient and patient-derived induced pluripotent stem cells (iPSCs).
Growing evidence indicates that ER dysfunction is involved in rare genetic disorders, including Wolfram syndrome, as well as more common diseases such as type 1 and type 2 diabetes retinal degeneration and neurodegenerative diseases. Thus, the potential public health implications of our research are considerable.
Regenerative and Gene Therapy
Dr. Urano’s research team is currently developing regenerative and gene therapy for diabetes, retinal dystrophy, neurodegeneration, and Wolfram syndrome. Dr. Urano hopes to treat his patients with such therapy in his endocrinology genetics clinic in the future.