Ocular gene therapy for choroideremia: clinical trials and future perspectives

Gene therapy offers the potential for targeted replacement of single gene defects in inherited retinal degenerations.

Choroideremia is an X-linked blinding retinal disease resulting from deficiency of the CHM gene product, REP1. The disease represents an ideal target for retinal gene therapy, as it is readily diagnosed in the clinic, relatively homogenous in phenotype and slow progressing, thereby providing a wide therapeutic window for intervention. Ongoing clinical trials of retinal gene therapy for choroideremia using an adeno-associated viral vector have demonstrated safety and early efficacy. We review the clinical characteristics of the disease with a view to interpreting the findings of gene therapy clinical trials and discuss future directions.

Choroideremia gene therapy has so far demonstrated good safety profile and early functional visual acuity gains in a proportion of trial participants, which appear to be sustained.