Overcoming the barriers to gene therapy in Leber congenital amaurosis

Research details

  • Type of funding: Fight for Sight / RP Fighting Blindness Small Grant Award
  • Grant Holder: Dr Jacqueline van der Spuy
  • Institute: UCL Institute of Ophthalmology
  • Region: London
  • Start date: April 2015
  • End Date: August 2015
  • Priority: Treatment
  • Eye Category: Inherited retinal


Leber congenital amaurosis (LCA) is a family of rare inherited eye conditions that lead to severe sight loss in young children. Research has shown that gene replacement therapy can rescue the eye’s light-detector cells (photoreceptors) and preserve sight in mice with LCA-like sight loss caused by mutations in the gene AIPL1.

Clinical studies have found that people with LCA and variations in AIPL1 can still show some electrical activity from the retina (the part of the eye that contains photoreceptors). This is important because it means there must still be some remaining photoreceptors that could potentially be rescued and preserved.

But before human gene therapy that targets AIPL1 can begin, researchers must overcome the hurdle that AIPL1 has lots of natural variations in its genetic code within the population. This can make it hard to tell whether the AIPL1 changes identified are causing the disorder, or if they are just part of this gene’s normal variation.

In this study Dr Jacqueline van der Spuy and co-investigators Professors Michel Michaelides and James Bainbridge aim to find out whether the AIPL1 variations in a group of LCA patients chosen for potential AIPL1-targeted gene therapy do in fact cause disease or not. This in turn will help identify the patients that could benefit from gene therapy.