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Background Choroideremia is an X-linked recessive disease that leads to blindness due to mutations in the CHM gene, which encodes the Rab escort protein 1 (REP1). We assessed the eff ects of retinal gene therapy with an adenoassociated viral (AAV) vector encoding REP1 (AAV.REP1) in patients with this disease. Methods In a multicentre clinical trial, six male patients (aged 35-63 years) with choroideremia were administered AAV.REP1 (0.6-1.0 × 10 10 genome particles, subfoveal injection). Visual function tests included best corrected visual acuity, microperimetry, and retinal sensitivity tests for comparison of baseline values with 6 months after surgery. This study is registered with, number NCT01461213. Findings Despite undergoing retinal detachment, which normally reduces vision, two patients with advanced choroideremia who had low baseline best corrected visual acuity gained 21 letters and 11 letters (more than two and four lines of vision). Four other patients with near normal best corrected visual acuity at baseline recovered to within one to three letters. Mean gain in visual acuity overall was 3.8 letters (SE 4.1). Maximal sensitivity measured with dark-adapted microperimetry increased in the treated eyes from 23.0 dB (SE 1.1) at baseline to 25.3 dB (1.3) after treatment (increase 2.3 dB [95% CI 0.8-3.8]). In all patients, over the 6 months, the increase in retinal sensitivity in the treated eyes (mean 1.7 [SE 1.0]) was correlated with the vector dose administered per mm-rfsti of surviving retina (r=0.82, p=0.04). By contrast, small non-signifi cant reductions (p<0.05) were noted in the control eyes in both maximal sensitivity (-0.8 dB [1.5]) and mean sensitivity (-1.6 dB [0.9]). One patient in whom the vector was not administered to the fovea re-established variable eccentric fi xation that included the ectopic island of surviving retinal pigment epithelium that had been exposed to vector. Interpretation The initial results of this retinal gene therapy trial are consistent with improved rod and cone function that overcome any negative eff ects of retinal detachment. These fi ndings lend support to further assessment of gene therapy in the treatment of choroideremia and other diseases, such as age-related macular degeneration, for which intervention should ideally be applied before the onset of retinal thinning.

Original publication




Journal article


The Lancet

Publication Date





1129 - 1137