Professor Jacqueline van der Spuy at UCL’s Institute of Ophthalmology will work with collaborators in Germany and Turkey to delve into the consequences of toxic accumulation of a molecule called cGMP. The three year project will use cell-based models of a very severe form of Leber congenital amaurosis (LCA) caused by mutations in the AIPL1 gene (LCA type 4), but cGMP accumulation also occurs in a number of other inherited retinal conditions, so understanding how it contributes to cell death could have much wider relevance.
The team will use cutting-edge techniques to follow up on clues about how excess cGMP impacts vital molecular pathways, with the aim of finding targets for therapeutic intervention. They also aim to test whether a particular potential drug can dampen cGMP’s toxic effects. The drug compound has already been extensively refined in other laboratory work, and Prof van der Spuy hopes that her project’s use of highly sophisticated disease models, based on human cells, would allow for rapid progress into clinical trials in LCA4, should the drug show promise.