First-of-a-kind study investigates genetic fault leading to severe sight loss

13 September 21

written by:

Anna Riley

(more articles)

Your support is offering patients with severe retinal diseases hope of future treatments using custom-designed drugs.

Professor Alison Hardcastle (left) is leading a world-class research team at UCL

Together with the Masonic Charitable Foundation, we are funding a first-of-its-kind study investigating a genetic fault that leads to severe sight loss and progressive blindness.

Researchers at the UCL Institute of Opthalmology, led by Professor Alison Hardcastle, are using the latest mRNA splicing technology and methods to learn how exactly these genetic faults cause sight loss and correct them. Ultimately, they hope this will lead to a new treatment.

Cone photoreceptors enable us to see in fine detail in daylight and perceive colour. The genes that code the light-sensing molecules in red and green photoreceptors are very similar and close together in the human genome, which makes them prone to genetic errors. The researchers have uncovered that 'skipping' of important parts of the genes is potentially a common cause of disease.

The team is using cutting-edge advances in stem cell techniques to grow model mini retinas and examine when and to what extent the cone photoreceptors are affected. They have already designed promising new drugs, called antisense oligonucleotides (AONs), that target where the skipping happens and enabel cone photoreceptors to make the correct version of the genes.

“Increasingly, new potential therapies are being developed for specific genetic faults, so called 'personalised medicine'. We're particularly enthusiastic about the potential for this treatment as it has shown effectiveness in initial trials for a severe form of early-onset retinal degeneration called Leber congenial amaurosis. We hope to pave the way to advance a therapy for patients with these retinal conditions.”

-Professor Alison Hardcastle, UCL Institute of Opthalmology