Advances in Gene Therapy for Wolfram Syndrome

SummaryThe Wolfram Syndrome (WS) is an early onset genetic disease (1/200 000) featuring diabetes mellitus and progressive optic neuropathy ensuing mutations in the WFS1 gene. To date, there is no treatment to stop the progression of the disease. We have characterized the visual impairment of 2 mutants animal models for WFS1 (Wfs1exon8‐/‐ and Wfs1E864K) and shown that these 2 models developed an optic atrophy. We started for 1 year intravitreous micro injections of therapeutic vector AAV2‐CMV‐WFS1 on 1 month‐old Wfs1exon8‐/‐. Our results showed that mice injected exhibited a stabilization of their visual acuity at 3 and 6 months post‐injection, and a decrease of optic disc pallor and optic nerve damage. These promising results demonstrate the validity of the pre‐clinical approach to treat Wolfram Syndrome by gene therapy and encourage further studies under a treatment for the Wolfram Syndrome patients.