New hope to prevent blindness in children with rare genetic disease

A new treatment that could prevent blindness in children with the CLN2 type Batten disease has been trialled by clinicians and researchers at GOSH and University College London Great Ormond Street Institute of Child Health (UCL GOS ICH).

Details of this landmark project were recently published in the Nature portfolio journal, Eye.

CLN2 disease is a rare degenerative genetic disorder affecting 30-50 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.

It first causes seizures, then gradual decline in a child's ability to walk, speak and see, alongside progressive dementia. Without treatment the life expectancy of a child with the disease is 10-12 years old.

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.

This agreement comes to an end in May 2025 so studies to explore how it works and 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 lost for children with the disease.

Clinical and research teams hoped to change this outcome in 2022 by using the left-over sample from the brain infusion to treat the eye.

The study was to establish if it was logistically possible to deliver the treatment in this way, and safe to do so, and is a great example of using innovative thinking to improve patients’ lives.

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.

Eight children who were currently on a treatment plan for Brineura and experiencing advanced damage to their retina took part in the study.

Children received the eye treatment under general anaesthetic on the same day they received their regular treatment.

Results showed that the treatment was safe and was effective in preventing more severe sight loss when delivered early enough.

Unfortunately, the majority of the children who were taking part in the study had lost too much of their sight for there to be a noticeable improvement in their sight loss but particularly for the children who were younger, with less severe sight loss, the treatment allowed them to keep more sight in the treated eye, compared to the untreated eye.

Professor Paul Gissen, honorary Consultant in Paediatric Metabolic Diseases at GOSH and the UCL GOS ICH 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."

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. Grace’s family were told there were no available treatments for the disease. However, around five months later they were given hope by the approval of Brineura for the condition under the NHS.

Grace had a port fitted into her brain in November and started her first treatment that December. Soon after starting the treatment, she regained the ability to walk.

She has since developed her speech and, while her verbal communication is not that of her peers, she can communicate in short sentences and is well, which the family are sure is due to the Brineura.

Mum Izabela said: “Grace just hasn’t deteriorated really, since starting Brineura, and in some areas like her mobility, she has actually improved.”

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 research study at GOSH.

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!”

Grace has Batten’s but she has similar likes to other girls her age. She loves her dogs, one of whom helped her to become toilet-trained, something often out of reach for children with Batten’s, and she loves soft toys.

Izabela said: “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.”

Liz Brownnutt, Chief Executive Officer of the BDFA said: “The current Managed Access Agreement for patients to continue to receive Brineura has recently been extended to May 2025 so that a long term solution can be sought. This is broadly good news but patients and families are still desperately seeking a resolution that can provide security for their futures.

"We want decision makers to take into account that with a small eye injection, and no extra costs of production, Brineura could also save the sight of the children affected, dramatically improving their quality of life and making this treatment even more of a game-changer for families.”

All research at GOSH is supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre.