Neurology. 2025 Oct 7;105(7):e214110. doi: 10.1212/WNL.0000000000214110. Epub 2025 Sep 9.
ABSTRACT
OBJECTIVES: Neuronal ceroid lipofuscinosis type 3 (CLN3) is a rare lysosomal storage disorder characterized by progressive neurodegeneration. No disease-modifying treatments are currently available. Miglustat, a substrate reduction therapy, has shown preclinical efficacy in CLN3 models (conference abstract). The aim of this study was to assess the long-term safety and clinical impact of miglustat in patients with CLN3 disease.
METHODS: This was an open-label, single-center study conducted at Bambino Gesù Children’s Hospital in Rome, Italy. Oral miglustat was titrated to 15 mg/kg/d or a maximum of 600 mg/d. Patients were assessed every 6 months using the Unified Batten Disease Rating Scale (UBDRS). The primary outcome was the annual rate of change in the UBDRS physical subscale. Clinical data were analyzed descriptively.
RESULTS: Six patients (33% female) with a median age of 20.34 years (interquartile range [IQR] 18.25-23.84) were treated and followed for a median of 3.9 years (IQR 3.32-4.34). The mean annual change in the UBDRS physical score was +1.96 points per year (SD ± 0.80). Miglustat was well tolerated, with only mild, self-limiting gastrointestinal side effects observed.
DISCUSSION: Miglustat showed a favorable safety profile and was associated with a slower rate of physical decline compared with historical controls. Limitations include small sample size, genetic heterogeneity, and open-label design.
PMID:40924969 | DOI:10.1212/WNL.0000000000214110
