The First LCA Gene Therapy Trials
The first clinical trial to test the then revolutionary treatment (Gene Therapy) for blindness in children was announced by researchers at UCL (University College London) in 2007. The trial, funded by the UK’s Department of Health, was the first of its kind and has had a significant impact on research into treatments for RP. RP Fighting Blindness also provided grant funding to support the trial.
The trial involved adults and children with condition called Leber congenital amaurosis (LCA), which is a type of inherited retinal degeneration. LCA is first symptomatic in early infancy with reduced central vision, nystagmus (involuntary to and fro movements of the eyes) and poor night vision. LCA is an autosomal recessive disorder which is caused by faults in more than 10 different genes. The gene therapy trial involved treatment of one specific form of LCA caused by faults in a gene called RPE65. This defect prevents normal function of the retina, the light-sensitive layer of cells at the back of the eye, resulting in severely impaired vision from infancy.
The technique used in the trial involved inserting healthy copies of the RPE65 gene into the cells of the retina to help them function normally (Gene Therapy Overview) in an operation in which specially modified viruses carrying a normal copy of the human RPE65 gene are injected beneath the retina. The virus gains entry into the retinal cells, thereby replacing the defective RPE65 gene with a normal copy of the gene, leading to improved vision. The intention was to demonstrate safety and to lay the ground for the development of gene replacement therapy for other recessive forms of RP.
The trial involved adults and children with condition called Leber congenital amaurosis (LCA), which is a type of inherited retinal degeneration. LCA is first symptomatic in early infancy with reduced central vision, nystagmus (involuntary to and fro movements of the eyes) and poor night vision. LCA is an autosomal recessive disorder which is caused by faults in more than 10 different genes. The gene therapy trial involved treatment of one specific form of LCA caused by faults in a gene called RPE65. This defect prevents normal function of the retina, the light-sensitive layer of cells at the back of the eye, resulting in severely impaired vision from infancy.
The technique used in the trial involved inserting healthy copies of the RPE65 gene into the cells of the retina to help them function normally (Gene Therapy Overview) in an operation in which specially modified viruses carrying a normal copy of the human RPE65 gene are injected beneath the retina. The virus gains entry into the retinal cells, thereby replacing the defective RPE65 gene with a normal copy of the gene, leading to improved vision. The intention was to demonstrate safety and to lay the ground for the development of gene replacement therapy for other recessive forms of RP.
Previous work using animal models had demonstrated that gene therapy can improve and preserve vision. During trials, the vision of dogs with the RPE65 defect was restored to the extent that they were able to walk through a maze; something they could not do before the treatment. As this trial was the first to treat an eye disease using administration of gene therapy vectors to human retinas, the team carried out extensive pre-clinical testing. The purpose of this trial was to find out how safe and effective the new intervention was in humans. Only time will tell whether the benefits observed in dogs will also be seen in humans in the long term.
A second research team, based at the University of Pennsylvania, USA, also in 2007, commenced a human clinical trial treating Leber congenital amaurosis. They too had previously shown that gene therapy can be effective in treating dogs with LCA caused by the RPE65 gene; with improved vision still being present at 5 years after treatment.
Promising results have since been reported by these and other teams in the UK and USA, strengthening the belief that Gene Therapy will prove a useful treatment option in the future for inherited retinal disorders.
A second research team, based at the University of Pennsylvania, USA, also in 2007, commenced a human clinical trial treating Leber congenital amaurosis. They too had previously shown that gene therapy can be effective in treating dogs with LCA caused by the RPE65 gene; with improved vision still being present at 5 years after treatment.
Promising results have since been reported by these and other teams in the UK and USA, strengthening the belief that Gene Therapy will prove a useful treatment option in the future for inherited retinal disorders.
