A new treatment that could prevent blindness in children with the CLN2 type Batten disease has been trialled by clinicians and researchers at UCL and Great Ormond Street Hospital (GOSH).
The study, published in Eye, found that the treatment was safe and effective in preventing more severe sight loss when delivered early enough.
CLN2 disease is a rare degenerative genetic disorder affecting between 30 and 50 children in the UK. It is caused by a change in a gene that is responsible for making a specific enzyme in the nervous system.
The disease first causes seizures, then gradual decline in a child's ability to walk, speak and see, alongside progressive dementia. The life expectancy for a child with this disease without treatment is about 10 to 12 years.
Since 2019, an enzyme replacement therapy called Brineura has been used to help prevent neurological deterioration in children with the disease under a managed access agreement.
However, this agreement will come to an end in May 2025, so studies exploring how it works and its benefits children who receive it are crucial.
Brineura is administered directly into the brain by a regular infusion. It has been shown to restore enzyme activity and slow the onset of disability.
However, this infusion into the brain does not prevent children going blind, as the enzyme cannot cross the blood-retina barrier. This means that the nerves in the eye cannot function and vision is still lost for children with the disease.
Now, clinicians and researchers at the UCL Great Ormond Street Institute of Child Health and GOSH are trying to prevent blindness in children with CLN2 Batten disease, by using the left-over sample of Brineura from the brain infusion to treat the eye.
The study involved eight children who were currently on a treatment plan for Brineura and experiencing advanced damage to their retina. Children received the eye treatment under general anaesthetic on the same day they received their regular infusion treatment.
Though the majority of the children who took part in the study had lost too much of their sight for there to be a noticeable improvement, for the children who were younger and with less severe sight loss, the treatment allowed them to keep more sight in their treated eye, compared to their untreated eye.
Lead researcher, Professor Paul Gissen (UCL Great Ormond Street Institute of Child Health and GOSH) said: "This work is a real team approach. Our Batten's patients are generally looked after by the metabolic team at GOSH and there has been a sad history of these children going blind.
"When Brineura was developed for the brain infusion, it was a great step forward. I supported the managed access agreement but we were still seeing these children lose their sight.
"By working with colleagues in ophthalmology, we proposed ideas, and developed a programme with Rob Henderson that we could deliver with his team at GOSH."
This work was supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre.
The programme was carried out with the permission of the pharmaceutical company so there was no extra cost for the treatment itself and the cost of the clinical time and procedure carried out under general anaesthetic was covered by the Batten's Disease Family Association (BDFA) and the CLN2 community, who raised over £200,000.
Patient story
In 2019 Grace's family noticed she was slurring her words and falling over a lot. Grace, then four years old, ended up in A&E after a particularly difficult trip to the zoo where she fell over around 50 times.
She was given an emergency MRI and was unfortunately diagnosed with CLN Type 2 Batten's disease soon after.
A few months later, Grace started receiving Brineura and regained her ability to walk. She has since also developed her speech and can communicate in short sentences.
The clinical team initially told the family that the treatment to the brain would not reach her eyes and Grace would sadly likely lose her sight, but then they were offered the opportunity to take part in the new research study.
Grace's mum, Izabela, said: "We can definitely see that the treated eye is better than the untreated one. She rubs the untreated eye more and you can see that she knows something isn't quite right but, because she has had one eye treated, she has managed to keep her sight and interacts with things like books and cartoons that she wouldn't be able to without her sight - the Gruffalo and Paddington are her favourite!"
Izabela added: "Brineura is not just saving Grace's life, it's making it better. We are hopeful that the treatment will be renewed under the NHS later this year and we hope that approval for treatment to the eye could follow after."
