Choroideremia (CHM) is a rare inherited retinal degeneration resulting from mutation of the CHM gene, which results in absence of functional Rab escort protein 1 (REP1). We evaluated retinal gene therapy with an adeno-associated virus vector that used to deliver a functional version of the CHM gene (AAV2-REP1).
THOR (NCT02671539) is a Phase 2, open-label, single-center, randomized study. Six male patients (51–60 years) with CHM received AAV2-REP1, by a single 0.1-mL subretinal injection of 1011 genome particles during vitrectomy. Twelve-month data are reported.
In study eyes, 4 patients experienced minor changes in best-corrected visual acuity (−4 to +1 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); one gained 17 letters and another lost 14 letters. Control eyes had changes of −2 to +4 letters. In 5/6 patients, improvements in mean (95% confidence intervals) retinal sensitivity (2.3 [4.0] dB), peak retinal sensitivity (2.8 [3.5] dB), and gaze fixation area (−36.1 [66.9] deg2) were recorded. Changes in anatomical endpoints were similar between study and control eyes. Adverse events were consistent with the surgical procedure.
Gene therapy with AAV2-REP1 can maintain, and in some cases, improve, visual acuity in CHM. Longer term follow-up is required to establish whether these benefits are maintained.