A large capacity vector to treat photoreceptor dystrophies

Brief Lay background

Stargardt disease is an inherited eye condition that causes progressive central sight loss due to damage to the macula – which is a small area in the centre of the retina, the specialised light-sensitive layer that lines the back of the eye.

The retina contains millions of light-sensing cells (photoreceptors), which are vital for healthy eyesight. In patients with Stargardt disease, the photoreceptors stop working or die – leading to sight loss that gets worse over time.

The condition is estimated to affect between one in 8,000 to 10,000 people in the UK.

What problem/knowledge gap does it help address

Stargardt disease is caused by faults in the ABCA4 gene, which provides the instructions for making an important protein that usually removes toxic by-products from photoreceptor cells. As a result, these substances build up and form a fatty waste product in and around the macula that start to affect the person’s vision. 

Gene therapy offers an opportunity to slow down or prevent sight loss for patients with Stargardt disease – by using a harmless virus to deliver a correct copy of the ABCA4 gene into their photoreceptor cells. 

This cutting-edge approach has been pioneered in the eye to treat several causes of inherited blindness, with some signs of success in clinical trials. But unfortunately, the viral vectors that have worked well for delivering genes into photoreceptors are not suitable for treating conditions associated with faults in large genes, including Stargardt disease. 

Aim of the project

The team has recently developed a modified viral vector that can carry larger genes and should also be more efficient at targeting photoreceptors. 

This project aims to demonstrate the clinical potential of this novel viral vector by using it to treat pre-clinical models of Stargardt disease.

Key procedures/objectives

1. Demonstrate the effectiveness of using this vector to deliver the ABCA4 gene into photoreceptors to treat a mouse model of Stargardt disease.
2. Test the efficiency of the novel vector at delivering the ABCA4 gene into photoreceptor cells – using ‘mini retinas’ generated from stem cells from a patient with Stargardt disease. 

Potential impact on people with sight loss

If successful, this new viral vector could help pave the way to the development of novel gene therapies for Stargardt disease, as well as several other inherited retinal conditions for which there is currently no cure. These cutting-edge treatments could help slow down or stop progressive sight loss, dramatically improving a patient’s quality of life.