Development of Methodology and Study Protocol: Safety and Efficacy of a Single Subretinal Injection of rAAV.hCNGA3 in Patients with CNGA3-Linked Achromatopsia Investigated in an Exploratory Dose-Escalation Trial

Hum Gene Ther Clin Dev. 2018 Sep;29(3):121-131. doi: 10.1089/humc.2018.088.

Abstract

Achromatopsia is an autosomal recessively inherited congenital defect characterized by a lack of cone photoreceptor function, leading to severely impaired vision. In this clinical study, achromatopsia patients were treated with a single subretinal injection of rAAV.hCNGA3 to restore cone function. The focus of this trial was on the safety of the treatment. After surgery, patients were monitored in eight extensive visits during the first year, followed by a 4-year follow-up period with annual visits. For essential complementation of the standard ophthalmological and systemic examinations, disease-specific methods were developed to assess the safety, efficacy, and patient-reported outcomes in this trial.

Keywords: AAV8; CNGA3; eye; gene therapy; subretinal injection.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Color Vision Defects / genetics*
  • Color Vision Defects / pathology
  • Color Vision Defects / therapy*
  • Cyclic Nucleotide-Gated Cation Channels / administration & dosage
  • Cyclic Nucleotide-Gated Cation Channels / adverse effects
  • Cyclic Nucleotide-Gated Cation Channels / genetics*
  • Dependovirus / genetics
  • Dose-Response Relationship, Drug
  • Female
  • Genetic Therapy / adverse effects*
  • Genetic Vectors / administration & dosage
  • Humans
  • Injections
  • Male
  • Middle Aged
  • Mutation
  • Retinal Cone Photoreceptor Cells / drug effects
  • Retinal Cone Photoreceptor Cells / pathology

Substances

  • CNGA3 protein, human
  • Cyclic Nucleotide-Gated Cation Channels