Gene therapy for Stargardt and other ABCA4-related diseases: lessons from RPE65-LCA trials

• Autor(a) principal: Silva, Nuno Filipe Aguiar
• Data de Publicação: 2010
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10316/18587
• topic: Distrofias hereditárias da córnea; Mutação

Stargardt disease is the most common among recessively inherited macular dystrophies, with 600 new disease cases diagnosed every year. It is caused by mutations in ABCA4, a photoreceptor-bound gene involved in normal visual cycle kinetics. The resulting disease phenotype, with accumulation of lipofuscin and other by-products in the retinal pigmented epithelium, is also recognized in the abca4 mouse model of the disease. Currently, Stargardt remains an incurable condition and there is little that can be done to improve the visual function of these patients. However, recent developments in ocular gene therapy will likely change this scenario. In the past decade, extensive research has been done in gene therapy for another form of retinal degeneration, Leber Congenital Amaurosis (LCA) associated with mutations in the RPE65 gene. Successful and sustainable rescue of vision in several animal models and human patients with RPE65-LCA, using AAV-mediated RPE65 gene replacement therapy, has led to the natural and rather easy application of the concept to Stargardt disease, and in fact, an ABCA4-based gene replacement trial is expected to enter Phase I/II development during 2010. If proven successful, this trial will provide unprecedented treatment possibilities for Stargardt disease and spectrum of retinal phenotypes associated with ABCA4 variation.