Gene therapy for the treatment of Wolfram Syndrome II

Wolfram Syndrome II is a progeria (early aging disease) characterized by accelerated senescence and death by mid-adulthood. There is no existing treatment. The disease affects multiple organ systems, and is caused by loss of function of the Cisd2 gene, which normally is expressed in many different cell types. As a result, it is thought that effective treatment of Wolfram Syndrome II will require multi-organ rescue of Cisd2 expression. Unfortunately, standard gene transfer technologies have not achieved sufficiently broad and uniform gene delivery to meet this therapeutic goal. We therefore created a new system (DAEUS) that overcomes the limitations of standard vector systems, and applied it successfully to ameliorate disease pathology in Cisd2 knockout mice. With Q-FASTR, we aim to perform dose-ranging studies and optimize component ratios of the DAEUS-Cisd2 system, ultimately deriving a dose-guiding model for achieving optimal therapeutic effects. This effort will de-risk our approach and lay a foundation for further development of multi-organ gene therapies.