The CLN2 gene, which is found on chromosome 11, produces an enzyme called tripeptidyl peptidase 1 the purpose of which is to break down proteins. The enzyme is insufficiently active in CLN2 disease and as a result those unbroken down proteins settle in the brain tissues. Developmental delay begins around the end of age 2. Children develop seizures and begin to gradually lose the ability to walk and speak. Brief, involuntary jerks in a muscle or muscle group (called myoclonic jerks) typically begin around age 4-5. By age 6 most children are completely dependent on their caregivers, and many will require a feeding tube. Most children with CLN2 disease die between the ages of 8–12 years. Until recently, the only treatment options for children with CLN2 were treatments that relieved symptoms of the condition, or palliative care in the final stages of the disease.
BioMarin undertook research and developed an enzyme replacement therapy trademarked as Brineura and became available with NHS England approval in September 2019 under a three year “Managed Access Agreement”.
The drug, which is called cerliponase alfa or Brineura, has been approved by the NHS following successful clinical trials at Great Ormond Street Hospital in collaboration with other centres around the world.
The therapy, which is infused directly into the brain via an implanted device, has been shown to restore enzyme activity and slows the onset of disability. In the trial, patients given cerliponase alfa showed 80% less decline in patients’ motor and language skills, when compared to the natural progression of the disease. The new therapy also reduced loss of brain tissue.
Professor Paul Gissen, NIHR GOSH BRC deputy theme lead for Novel Therapies and lead investigator at GOSH, said at the time of launch of the drug:
“The research shows that this cutting-edge therapy can make a huge difference for patients with this devastating condition. Until now there have been no drugs to treat Battens Disease so we are delighted that the treatment has been made available”.
Professor Gissen recruited four GOSH patients to the initial clinical trial and treated several more patients and siblings as part of an expanded access study leading to an announcement by NHS England on 11 September 2019 permitting the treatment to be made available to all suitable children by Christmas 2019.
There are now 19 children from 16 families undergoing the regular two weekly infusion treatments. It had been hoped that during 2020 it would be possible to enable other sites to undertake the treatment as at the moment there are lengthy journeys for some families as 12 of the families live in the Midlands or North of England. As further diagnoses of CLN2 are made it is anticipated that the numbers will increase.
With effect from 12 October 2020 the Scottish Medicines Consortium has recommended the use of Brineura in Scotland utilising a new ultra-orphan medicine pathway for appraising ultra-rare treatments. It is hoped that as a result of this recommendation that any new CLN2 diagnoses in Scotland will be able to benefit very quickly from the treatment.