Miglustat does not impact clinical progression in patients with spastic paraplegia type 11

Spastic paraplegia type 11 (SPG11) is a progressive neurological condition with no treatment. Possible involvement of abnormal ganglioside metabolism has been reported in mouse and human cells. Preclinical data in zebrafish and fruit fly models of the disease indicate that miglustat can improve biochemical parameters and locomotion. We assessed the short-term safety of oral miglustat in patients with SPG11. This was an open-label, single center, non-randomized, phase II study. All patients received miglustat orally (4 weeks 100 mg/tid and 8 weeks 200 mg/tid). The primary outcome was the frequency of adverse events (AEs), particularly and severe AEs (SAEs), emerging in the course of the study. As secondary outcomes we measured clinical severity scores, functional tests, and biomarkers at 3 and 6 months. Twelve-week treatment with miglustat was adequately tolerated, with only minor AEs and no SAEs reported. With a few exceptions, the treatment did not seem to impact neuromotor function in patients with SPG11. Although it showed an acceptable safety profile and no SAEs, miglustat did not significantly modify plasma sphingolipid and ganglioside profiles. Its potential therapeutic impact remains low.