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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) and Moorfields Eye Hospital 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 with many similarities to RP, albeit of earlier onset. 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 17 different genes (August 2013). 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 ('viral vector') 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.

Figure 24 LCA Gene Therapy Trial - Illustration

Figure 24 LCA Gene Therapy Trial - Illustration

Figure 25 LCA Gene Therapy Trial - Laboratory

Figure 25 LCA Gene Therapy Trial - Laboratory

Figure 26 LCA Gene Therapy Trial - Operation

Figure 26 LCA Gene Therapy Trial - Operation

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 viral 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.

The results results that have been reported by these and other teams in the UK and USA, have been encouraging, demonstrating a good safety profile and evidence of improved retinal function which appears to be maintained at least to 3 years in some patients. Further RPE65 trials are planned in both the USA and UK in the near future.

These findings strengthen the belief that Gene Therapy will prove a useful treatment option for inherited retinal disorders.


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