The aim is to develop a novel therapy for late-onset retinal degeneration (L-ORD), a rare but severe form of human retinal degeneration causing extensive visual loss, for which there is no treatment. L-ORD is caused by genetic changes (mutations) in the C1QTNF5 gene, a gene of previously unknown function, strongly expressed in the retinal pigment epithelium (RPE), which supports photoreceptor health. L-ORD is inherited in an autosomal dominant manner, with a 1 in 2 risk to offspring of affected individuals. We propose to correct the most common C1QTNF5 mutation in cultured RPE cells using “gene editing” reagents carried by an inactivated viral vector that is capable of entering RPE cells and correcting the causal mutation. After constructing the editing vector, we will test it in the laboratory context by measuring its gene correction efficiency in our established stem cell-derived and other RPE cell models of L-ORD. In parallel, we will recruit L-ORD patients from 3 clinical centres, each of whom carries the commonest C1QTNF5 mutation and we will characterise the disease in depth. This will determine the most suitable stage of the disease for administering such a therapy by injection under the retina and how best to monitor the value of treatment to the L-ORD patients.
Professor Baljean Dhillon describes what late onset retinal degeneration is in a short video.
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John Playfair and Gordon Hastie give their perspective of L-ORD