Choroideremia: Toward Regulatory Approval of Retinal Gene Therapy.

Choroideremia is an X-linked inherited retinal degeneration characterized by primary centripetal degeneration of the retinal pigment epithelium (RPE), with secondary degeneration of the choroid and retina. Affected individuals experience reduced night vision in early adulthood with blindness in late middle age. The underlying CHM gene encodes REP1, a protein involved in the prenylation of Rab GTPases essential for intracellular vesicle trafficking. Adeno-associated viral gene therapy has demonstrated some benefit in clinical trials for choroideremia. However, challenges remain in gaining regulatory approval. Choroideremia is slowly progressive, which presents difficulties in demonstrating benefit over short pivotal clinical trials that usually run for 1-2 years. Improvements in visual acuity are particularly challenging due to the initial negative effects of surgical detachment of the fovea. Despite these challenges, great progress toward a treatment has been made since choroideremia was first described in 1872.