A major form of RP is caused by defects in components of the “spliceosome”, an important and complex structure within cells. The spliceosome edits unwanted or nonsensical passages out of a set of genetic instructions so that only intelligible code remains for the cell to use. One of the most common causes of RP is a fault in a group of genes that regulate this process.
Thanks to earlier funding from Retina UK, Prof Lako and her team have used stem cell technology to generate retinal cells from patients with mutations in a key gene involved in the splicing process (PRPF31), and have demonstrated that retinal pigmented epithelial (RPE) cells and photoreceptors are affected at the structural and functional level.
The newly funded project aims to develop a PRPF31 gene therapy to increase levels of healthy PRPF31, and use the retinal cell model to assess the therapy’s efficacy in restoring RPE and photoreceptor function. This highly collaborative study, involving four institutions across the UK and Germany, provides a unique opportunity for rapid proof-of-concept, leading to the potential for rapid translation into a Phase I/II clinical trial for PRPF31 RP patients as an immediate outcome. Between them, faulty spliceosome genes are a relatively major cause of RP, so the outcomes of this project should also be applicable to the development of treatments for a wider proportion of our community.