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Urano Fumihiko – Washington University: Study of the the efficacy of a new small molecule (JTV-519 and oxidized form of JTV-519) in mouse and rat models of Wolfram syndrome.


2016 - Endoplasmic reticulum (ER) participates in so many cellular tasks that trouble can ensue when it stops working properly, including ß cell death in type 1 and type 2 diabetes, neurodegeneration, and retinal cell degeneration. Despite the underlying importance of ER dysfunction, there is no effective treatment targeting the ER due to the complex etiologies of such disorders. Our strategy for overcoming this challenge is to focus on genetic disorders in which mutations in single genes are involved in ER dysfunction and disease manifestations. Wolfram syndrome is a rare autosomal recessive genetic disorder characterized by juvenile-onset diabetes, retinal degeneration, and neurodegeneration. Wolfram syndrome is considered as a prototype of ER disorder. Its monogenic etiology makes Wolfram syndrome more amenable to discover drugs targeting ER dysfunction than other common conditions in which multiple factors typically interact to produce the disease manifestations. We propose to develop novel drugs targeting the ER for the treatment of Wolfram syndrome. Our study on Wolfram may lead to a breakthrough for the treatments of common diseases, including diabetes, neurodegeneration, and blindness.

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