LOS ANGELES – Intraventricular administration of cerliponase alfa seemed to slow the rate of motor and language decline in an open-label trial of 23 children with neuronal ceroid lipofuscinosis type 2 disease.
Neuronal ceroid lipofuscinosis type 2 disease (CLN2), a form of Batten’s disease, is a rare lysosomal storage disorder that causes progressive dementia in children. Patients have pathogenic variants in the gene encoding lysosomal enzyme tripeptidyl peptidase 1 (TPP1). Without functioning enzyme, lysosomal storage material accumulates in neurons throughout the CNS and retina.
Symptoms start at 2-4 years with seizures and language delays, followed by rapid motor, language, and cognitive declines, and blindness. Children die in early adolescence. Treatment is symptomatic; there are no approved therapies.
The idea of the study was to replace the enzyme in the CNS with cerliponase alfa, a recombinant form of TPP1. Twenty-four children aged 3-16 years received 30 mg, 100 mg, or 300 mg intraventricular infusions every 2 weeks during the dose-finding phase of the open-label trial; they were then switched to 300 mg infused over 4 hours every 14 days for at least 96 weeks. One child dropped out after the first dose in the study, but the others continued.
The investigators used Ommaya or Rickham ventricular reservoirs to deliver the enzyme, which were more convenient than intrathecal administration, said investigator Emily de Los Reyes, MD, a pediatric neurologist at Nationwide Children’s Hospital, Columbus, Ohio.
The primary outcome was the time until a 2-point decline on the motor and language scores of the CLN2 Clinical Rating Scale, with 0 representing no function and 6 representing normal function in both domains. The mean unadjusted rate of decline in the motor-language score per 48-week period was 0.27 points in treated patients, versus 2.12 points in 42 historical controls (P less than .001). The treatment difference at 96 weeks was about 3.3 points. There was also a decrease in seizure severity and frequency.