Novel therapy reduces disease progression in rare neurodegenerative condition

A pioneering new treatment trialled at Great Ormond Street Hospital (GOSH) reduces disease progression by 80 per cent for patients with the rare neurological disorder CLN2.CLN2 is a form of Batten disease and is caused by an error in the TPP1/CLN2 gene, which means that the TPP1 enzyme is defective. The condition affects between 30 and 50 children in the UK, and causes recurrent seizures, difficulty coordinating movements and progressive dementia.

In this phase I/II multinational trial, cerliponase alfa, a recombinant form of the TPP1 enzyme designed to restore enzyme activity, was infused directly into the brain of 23 patients from across the world.  Professor Paul Gissen, National Institute for Health Research (NIHR) GOSH Biomedical Research Centre (BRC) deputy theme lead for novel therapies, recruited four GOSH patients to the trial who were treated at the NIHR GOSH Clinical Research Facility (CRF) under the care of our expert novel therapies research nursing team.

After a year, patients showed 80% less decline in their motor and language skills, when compared to the natural disease progression. Cerliponase alfa also reduced loss of cortical grey matter in the brain.

Following the release of positive 48 week results by Biomarin in 2016, the European Medicines Agency has given a positive opinion for the use of cerliponase alfa in CLN2 patients of all ages and US Food and Drugs Administration (FDA) approval was also obtained for CLN2 patients aged 3 years and above. The study findings, which were recently published in New England Journal of Medicine, forms part of evidence submitted for National Institute of Health and Care Excellence (NICE) review.

In addition, an early access (compassionate use) programme was implemented with a further six CLN2 patients enrolled on an extension study as part of NHS care at GOSH. Studies are now ongoing to examine the safety of cerliponase in CLN2 patients below the age of two years and to assess the drug’s long-term effects. A further study is now assessing disease progression in siblings of children enrolled on the initial phase 1/2 trial, also in partnership with Biomarin pharmaceuticals.

This ‘first in child’ study and the use of a novel intraventricular device to administer the drug infusion by highly-qualified clinical practitioners exemplifies the GOSH CRF’s research strategy of developing capacity and capability to support high intensity early-phase clinical trials in children.

Previously there were no disease-specific therapies for CLN2 patients given antiepileptic drugs to reduce seizures as well as palliative care of the final stages of the disease. However, patients usually died before the age of 10. This research is therefore an important step forward for CLN2 patients and their families.