All but one child experienced convulsions, over two-thirds pyrexia, and almost two-thirds vomiting and hypersensitivity. About half developed upper respiratory tract infections, and about half had increased CSF white-cell counts. There were also cases of device leakage, and two children developed infections detected by CSF monitoring, without symptoms of meningitis. Both continued treatment after removal of the intraventricular device, followed by antibiotics, and device replacement.
Fourteen patients (58%) had at least one grade 3 adverse event, and there was one grade 4 event: status epilepticus deemed unrelated to the study. Side effects resolved on their own or responded to medical management. There were no deaths, study discontinuations, or dose reductions.
The mean age in the study was 60 months, about two-thirds of the patients were girls, and CLN2 diagnosis was confirmed by genotyping. Almost all the children had seizure histories. The majority were moderately advanced at baseline, with motor-language scores of 3 out of 6 in 11 patients.
An audience member asked Dr. de Los Reyes if there would be even more benefit by starting treatment before children became symptomatic. “I think all the neurologists in this group, we know that the earlier the treatment for rare diseases, the better the response,” she said.