Gene therapy treats rare form of blindness in infants

A new gene therapy improves sight in children with a rare genetic disease that causes blindness.

Four children affected by Leber congenital amaurosis (LCA), a rare genetic disease that leads to blindness in the first years of life, have partially regained vision after treatment with a new gene therapy. A team of doctors at Moorfields Eye Hospital and University College London (UCL), injected functional copies of a gene that is defective in LCA patients in the back of their eye, and monitored their vision in the following years. Children that were only able to distinguish light and darkness can now recognise toys and other items.

'We have, for the first time, an effective treatment for the most severe form of childhood blindness' said Michel Michaelides, professor of ophthalmology at UCL Institute of Ophthalmology, and first author of the study published in The Lancet. 'The outcomes for these children are hugely impressive and show the power of gene therapy to change lives.'

LCA is caused by mutations in a gene called AIPL1, which is responsible for the maintenance of the retina – a thin layer of cells located in the back of our eyes. The retina perceives light, shapes and colours and transmits these visual stimuli to the brain in the form of electric signals. When AIPL1 is defective, retinal cells rapidly degenerate and die, causing severe vision loss.

The gene therapy developed in this study delivered a healthy copy of AIPL1 to the retina, by using adenoviruses as messengers. These viruses can penetrate cells and replace defective genes with healthy ones through a cut-and-paste mechanism.

One of the children who received the treatment was Jace, from Connecticut. His mother DJ explained: 'After the operation, Jace was immediately spinning, dancing and making the nurses laugh. He started to respond to the TV and phone within a few weeks of surgery and, within six months, could recognise and name his favourite cars from several metres away.'

His father Brendan added: 'Pre-surgery, we could have held up an object near his face and he wouldn't be able to track it at all. Now he's picking things off the floor, he's hauling out toys, doing things driven by his sight that he wouldn't have done before.'

The clinical study was primarily designed to evaluate whether early intervention by gene therapy was safe. As such, the first four children (aged between 12 and 34 months) were administered the therapy to one eye only in case of any potential safety issues.

The children were monitored for three to four years to also assess whether the therapy could improve their condition. All four children saw improvements in the treated eye, but lost sight in their untreated eye. Further monitoring of the children who received the gene therapy will assess the long-term impact of the treatment.

'Sight impairment in young children has a devastating effect on their development. Treatment in infancy with this new genetic medicine can transform the lives of those most severely affected' added James Bainbridge, professor of retinal studies at UCL Institute of Ophthalmology and senior author of the study.

Gene therapy for another rare type of LCA retinal dystrophy, caused by mutations in the RPE65 gene, has been available on the NHS since 2020 (see BioNews 1036).