CHANGES IN RETINAL SENSITIVITY AFTER GENE THERAPY IN CHOROIDEREMIA

Retina. 2020 Jan;40(1):160-168. doi: 10.1097/IAE.0000000000002360.

Abstract

Purpose: 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).

Methods: 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 10 genome particles during vitrectomy. Twelve-month data are reported.

Results: 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] deg) were recorded. Changes in anatomical endpoints were similar between study and control eyes. Adverse events were consistent with the surgical procedure.

Conclusion: 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.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Choroideremia / physiopathology
  • Choroideremia / therapy*
  • Dependovirus
  • Genetic Therapy*
  • Genetic Vectors
  • Humans
  • Male
  • Middle Aged
  • Parvovirinae / genetics*
  • Retina / physiopathology*
  • Visual Acuity / physiology
  • Visual Field Tests
  • Visual Fields / physiology
  • Vitrectomy

Substances

  • Adaptor Proteins, Signal Transducing
  • CHM protein, human

Supplementary concepts

  • Adeno-associated virus-2