Cerliponase alfa for treating neuronal ceroid lipofuscinosis type 2

Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rare genetic disease caused by deficiency of the enzyme called tripeptidyl peptidase 1 (TPP1). It is 1 form of neuronal ceroid lipofuscinosis, also known as Batten disease. CLN2 is inherited as an autosomal recessive disorder, which means that both chromosome copies carry mutations in the CLN2 gene, and both parents are unaffected carriers. A deficiency of TPP1 results in abnormal storage of proteins and lipids in neurons and other cells. Accumulation of these proteins and lipids prevents the cells from functioning as they should.

CLN2 progresses rapidly and predictably from presentation in late infancy to death by early adolescence. It is characterised clinically by a decline in mental and other capacities, epilepsy and sight loss because of retinal degeneration. Histopathologically, there is intracellular accumulation of ceroid lipofuscin in the neuronal cells of the brain and retina. Symptoms in children with CLN2 appear in the second year of life and can then progress rapidly with a decline in speech, the onset of seizures, loss of mobility, involuntary muscle spasms and, later on, visual impairment leading to blindness. Ultimately, the child will become totally dependent on family and carers for all their needs. Life expectancy is around 8 years to early adolescence.

The exact prevalence and incidence of CLN2 is unknown. It is estimated that, in the UK, around 3 to 6 children are diagnosed each year and currently around 30 to 50 children are living with the condition.

There is no cure or life-extending treatment option available for CLN2. Clinical management focuses on symptom control, monitoring and preventing complications, and palliative care. The aim is to maintain function for as long as possible and to improve quality of life. This involves a multidisciplinary and multi-agency team working to control symptoms and complications such as malnutrition, gastroesophageal reflux, pneumonia, anxiety, Parkinsonian symptoms and dystonia, using medication and physical therapy. Children often need multiple medications, and clinicians need to balance symptom control with adverse effects and treatment interactions.