Gene therapy for Stargardt disease

Stargardt disease is the most common cause of macular degeneration and central visual loss in young people. Currently, there is no known effective treatment that can prevent or reverse the vision loss in this disease. The disease is caused by mutations in the photoreceptor‐specific ABCA4 gene cording for a protein involved in the active transport of retinoids from the photoreceptors to the underlying retinal pigment epithelium to initiate the visual cycle. Pre‐clinical studies on animal model of Stargardt disease have shown effects on subretinal administration of viral vectors containing the human ABCA4 gene upon liposfuscin accumulation, the hallmark of the disease, thus providing a proof‐of‐concept for gene therapy. Indeed, the first‐ever gene‐based therapy Phase I/II clinical trial for treatment of Stargardt disease, StarGen™, is currently underway (NCT01367444) at the Casey Eye Institute, Oregon Health & Science University, US and the Centre Hospitalier Nationale d'Ophthalmologie des Quinze‐Vingts, Paris, France. We will discuss the principle and issues raised by the current trial as well as potential alternative therapies.