Open-label evaluation of oral trehalose in patients with neuronal ceroid lipofuscinoses.

The neuronal ceroid lipofuscinoses (NCLs) are incurable pediatric neurodegenerative diseases characterized by accumulation of lysosomal material and dysregulation of autophagy. Given the promising results of treatment with trehalose, an autophagy inducer, in cell and animal models of NCL, we conducted an open-label, non-placebo-controlled, non-randomized 12-month prospective study in NCL patients receiving oral trehalose (4 g/day). All were treated with a commercially available formulation for 6 months, followed by a 6-month washout. The primary endpoint was the presence of severe adverse reactions during treatment; secondary endpoints were clinical changes documented using the validated Unified Batten Disease Rating Scale and the Hamburg scale. Leveraging on our recent multiomic studies identifying convergent biomarkers in NCLs, fluid biomarker changes were taken as additional secondary endpoints. Of the 17 patients enrolled, 11 completed the study. Oral intake of trehalose in NCL patients with different genetic forms and at different disease stages was found to be well tolerated over 6 months. Oral trehalose is associated with subjective benefits reported by caregivers, but not with improvement or worsening on clinical scales. Analysis of potential biomarkers demonstrated significant differences between patients and controls at baseline, but we observed no modifications over time, or correlations with clinical scales and treatment. In our pilot experience in a heterogeneous disease group of NCL, oral trehalose seemed safe for patients. While subjective improvements were reported by caregivers, larger multicenter randomized placebo-controlled studies, and perhaps additional clinical tools covering multiple functions affected by the disease, will be needed to identify possible improvements in clinical scale scores and biomarkers.