Late-onset inherited retinal disease is a cause of severe visual loss in the older population. Late-onset disease results from a slower-onset retinal degeneration and is more commonly linked to dominant inherited disease. Dominant diseases are usually caused by a single faulty gene which disrupts normal retinal function.
One approach to treat a dominant disease is to use gene editing. By targeting the faulty gene using CRISPR-Cas9 gene editing the faulty gene can be removed allowing the retina to function properly with the remaining normally functioning gene. We have recently developed a model of retinal degeneration caused by the disease late-onset retinal degeneration (L-ORD).
This dominant disease causes blindness in patients in their 60s and shares many similarities with age-related macular degeneration. We have recently completed a series of long-term clinical natural history studies to describe the progression of disease in eyes of patients to identify the best time to treat patients. This work is in close collaboration with Professor Baljean Dhillon (University of Edinburgh) and Dr Andrew Browning (Newcastle Hospitals NHS trust).
Recently, we also developed a model in a dish of L-ORD using patient stem cells. We found that patient cells develop a marked immune reaction similar to that seen in in the diseased retina.
We corrected the mutation using CRISPR gene editing and found that the cells normalized their immune activation, providing a powerful ‘Disease in a dish’ model.
We have recently developed a virus to deliver gene editing technology and are also testing other gene modifying approaches to treat our model. If successful, the plan is to translate this strategy to treat patients who we have already characterized in our long-term natural history studies.
Additionally, we are currently carrying out research with cells carrying mutations with EFEMP1 and TIMP3 mutations to see if these can be treated with gene modification.