LAUSR

BackgroundNiemann-Pick disease, type C1 (NPC1) is a neurodegenerative condition that arises from mutations of NPC1 and is often diagnosed in children. Recently, several drug trials have been implemented to minimize neurodegeneration, including a trial of 2-hydroxypropyl-β-cyclodextrins (VTS-270).ObjectivesThe current study extends findings from a previous report of 18 months of disease severity data by describing neuropsychological outcomes over the course of 36 months post-baseline.DesignAn open-label, dose-escalation phase I/IIa study of VTS-270 was performed in participants with NPC1 aged 4–23 years.MethodsFourteen participants were sequentially assigned to receive monthly initial intrathecal VTS-270 at doses of 50, 200, 300, or 400 mg per month. After initial dosing, participants were dose-escalated (to 600 or 1200 mg) as tolerated. Participants were evaluated at 6-month intervals using a standardized neuropsychological battery, including tests of cognition and adaptive behavior. A random effects model with restricted maximum likelihood estimation was constructed for each outcome, and the slope was the parameter of interest.ResultsFindings based on IQ scores and both standard scores and age equivalents of adaptive functioning indicate that there were not meaningful declines in these areas during the study period. The average annualized change in Full Scale IQ was negative: B = − 1.28, standard error (SE) = 0.70, t(34.2) = − 1.83, p = 0.076. The Vineland-II Adaptive Behavior Composite standard score decreased by 1.76 points per year [SE = 0.67, t(59.1) = − 2.62, p = 0.011], but annualized slopes for each of the domain age equivalents were positive: Communication [B = 0.71, SE = 3.12, t(60.7) = 0.23, p = 0.82], Socialization [B = 2.99, SE = 2.92, t(60.4) = 1.03, p = 0.30], Daily Living Skills [B = 2.76, SE = 2.76, t(60.3) = 1.18, p = 0.24], and Motor Skills [B = 1.42, SE = 0.94, t(50.5) = 1.51, p = 0.14], indicating not worsening but slower-than-average acquisition of skills.ConclusionIn conjunction with previous findings, these results provide support for the slowing of disease progress up to 36 months post-initiation of intrathecal VTS-270.RegistrationClinicalTrials.gov identifier NCT01747135: Hydroxypropyl Beta Cyclodextrin for Niemann-Pick type C1 Disease.