Finding a way to correct genes that cause disease
Prof Michael Cheetham | GR000193
Inherited genetic changes are a major cause of blindness. We’re funding research exploring whether antisense gene therapy could treat inherited eye conditions, focusing first on Stargardt Disease.
Inherited genetic changes are a major cause of blindness, particularly in diseases that affect the function of the retina (at the back of the eye) by leading to a loss of function in essential components of retinal cells.
Stargardt disease is the most common cause of inherited central vision loss, affecting more than one in 10,000 people. Stargardt is caused by inherited mutations in the ABCA4 gene.
Traditional genetic tests have revealed errors in the ‘coding’ parts of these genes, however recent advances in testing, such as whole genome sequencing, have shown that this may not be applicable to up to 20 per cent of ABCA4 patients. Instead, research suggests that there may be an error present in the non-coding regions of the genes (called ‘introns’) that sit in between the coding regions (called ‘exons’).
What is Stargardt disease?
Stargardt disease develops when an area of light sensitive cells at the back of your eye (the macular) begins to waste away. It is a genetic condition and can cause severe sight loss.
The macular is part of your retina, and it’s responsible for detailed vision - you would need it to watch TV or read, for example.
In Stargardt disease, the cells in the macular begin to die. This leads to a loss of detailed vision and a reduced ability to see colour, as well as blurriness and blind spots.
The macular is only responsible for central vision, so Stargardt disease doesn’t usually cause loss of peripheral vision. However, many people with Stargard disease will end up with severe vision loss.
1 in 9,000
Stargardt disease affects one in every 8,000-10,000 people
Since Stargardt is an inherited genetic condition, symptoms usually begin to show before the age of 20.
Currently there is no treatment or cure for Stargardt disease. People suffering with Stargardt disease should wear UV-blocking sunglasses to protect their eyes from further damage.
Trials are currently in progress investigating whether stem cells could be used to repair the macular and restore sight to patients with Stargardt disease.
Funding a solution
Led by Professor Mike Cheetham, a team of researchers will look at a type of gene therapy called antisense therapy (AON), which aims to correct the fault in the gene that causes the disease.
The team will grow retina cells from patients with Stargardt disease in the laboratory so they can deliver small pieces of DNA to the cells and try and correct the mistake. They will do this by using an artificial ‘mini-gene’ and screening a range of AONs for their ability to correct the genetic error.
Impact and outcome
This research aims to provide proof of concept and to the necessary robust data to underpin and advance further research, and ultimately develop gene therapy.
Research project grant
Prof Michael Cheetham
Macular degeneration | Genetics | Inherited eye disorders