Gene Therapy & Pharmacotherapy for Inherited Retinal Disease: Current Status

Purpose To describe the rationale for gene therapy and pharmacological treatments in retinal dystrophies, and to show a few examples of the undergoing trials. Methods Gene therapy can be applied to complement (in loss‐of‐function mutation) or to suppress (in gain‐of‐function mutation) a mutated gene, in order to correct the specific defect linked to this gene. Gene therapy can also be used to in situ produce a protein whose properties will modify the course of the disease. In a similar way, pharmacological drugs can supplement the metabolic defect linked to a specific gene, or can facilitate photoreceptor survival and/or function whatever the genetic defect. Results Conditions (photoreceptor dysfunction and degeneration, rate of degeneration, stage at disease diagnosis) to which gene therapy can be applied will be reviewed. Retinal dystrophies linked to RPE65 mutations provide good examples of both gene therapy by complementation and pharmacological therapy by supplementation. Gene repair is a promising approach to reverse mutations into the correct sequence. Rapid descriptions of ongoing trials for congenital achromatopsia, Stargardt disease and retinitis pigmentosa will be showed. Conclusion Future developments of therapeutic interventions will depend on accurate molecular diagnosis, knowledge of pathophysiological mechanisms and improvement in drug ocular delivery.