A group of eight children at Great Ormond Street Hospital (GOSH) and UCL GOS Institute of Child Health (ICH), all born with CLN2-type Batten disease – a rare and fatal genetic disorder that would otherwise likely leave them blind by the time they hit elementary school – have just become the first people in the world to trial a pioneering new treatment aimed at saving their sight.
The treatment is being administered on a compassionate use basis – in other words, it’s not approved for this use, but neither is any other treatment – and these children “have no other option,” Professor Paul Gissen, honorary Consultant in Paediatric Metabolic Diseases at GOSH and ICH, said in a statement.
“Treatments given under compassionate use are always subject to very rigorous assessment, and at GOSH we have a long history of pioneering these carefully-considered treatments,” Gissen explained. “If successful, we hope our work on this program can pave the way to saving the sight of more children with this disease to preserve their quality of life for as long as possible.”
Now, no disease is fun, but some are especially nasty. And Batten disease – in particular CLN1- and CLN2-type Batten disease – is without doubt one of the nastiest. It’s incredibly rare – around two to four children are born each year with the condition – but it’s incurable, quickly degenerative, and fatal. Children affected by the disease will, starting from the age of one or two years old, suffer from increasingly uncontrollable seizures. They will become less steady on their feet, and fall more frequently; gradually, they lose the ability to walk, play, and talk. Their arms and legs jerk and eventually become stiff; their vision deteriorates entirely, and they progressively succumb to dementia. By the age of six, they are usually completely dependent on their family and carers for their day-to-day survival – and by the age of around 10 to 12 years old, they will likely be dead.
It’s only very recently that there has been any kind of treatment for CLN2-type Batten disease: a drug called cerliponase alfa or Brineura, which is administered by regular infusion directly into the brain. This is an enzyme replacement therapy: the disease is caused by a defect in a gene that’s responsible for making enzymes that are needed for cleaning out all the junk and waste from our cells, and so the treatment is designed to replace that enzyme, thus slowing the disease’s progress.
This treatment has been shown to delay the onset and severity of symptoms, but so far it’s had one big drawback: because it’s delivered via an infusion into the brain, it hasn’t been able to treat the visual symptoms. Thanks to the particularly strong blood-retinal barrier, the enzyme is unable to reach the nerves in the eye, and so even those children lucky enough to receive treatment still end up going completely blind at a heartbreakingly young age.
“We have watched our son Ollie go blind, and now the same is starting to happen to Amelia,” said Lucy Carroll, the mother of two children with CLN2-type Batten disease. “But we have been given this chance, this hope. To save a child's sight would be incredible, and make such a big difference to Amelia’s quality of life.”
The new treatment is pretty simple, really: the clinicians are using a tiny amount of the drug left over from the brain infusion, and injecting it straight into the back of the children’s eyes. That may sound icky, but it’s actually a very common and straightforward procedure – and, hopefully, it will provide the eye nerves with the enzymes they are otherwise unable to access. The kids involved in the study are currently receiving just one dose every two months, in one eye only – the researchers involved will monitor the treatment and the patients carefully for any side effects and progress.
If the treatment is successful, the team at GOSH and ICH believe it could be transformative for children across the world who are affected by CLN2-type Batten disease. The results of the scheme should be discovered after a year, when the multidisciplinary team plan to compare the difference in vision between the eye which received the treatment and the eye which didn’t.
“Like so many other families of children with this awful disease, we knew we had to do everything we could,” said Dr Rahul Dubey, the father of eight-year-old Kavyansh, already nearly blinded by the disease.
”We feel extremely lucky that Kavy has some chance to keep the little sight he has left,” Dubey added. “It means everything for us.”