Efficacy and safety of N-acetyl-L-leucine in Niemann-Pick disease type C

J Neurol. 2022 Mar;269(3):1651-1662. doi: 10.1007/s00415-021-10717-0. Epub 2021 Aug 13.


Objective: To investigate the safety and efficacy of N-acetyl-L-leucine (NALL) on symptoms, functioning, and quality of life in pediatric (≥ 6 years) and adult Niemann-Pick disease type C (NPC) patients.

Methods: In this multi-national, open-label, rater-blinded Phase II study, patients were assessed during a baseline period, a 6-week treatment period (orally administered NALL 4 g/day in patients ≥ 13 years, weight-tiered doses for patients 6-12 years), and a 6-week post-treatment washout period. The primary Clinical Impression of Change in Severity (CI-CS) endpoint (based on a 7-point Likert scale) was assessed by blinded, centralized raters who compared randomized video pairs of each patient performing a pre-defined primary anchor test (8-Meter Walk Test or 9-Hole Peg Test) during each study periods. Secondary outcomes included cerebellar functional rating scales, clinical global impression, and quality of life assessments.

Results: 33 subjects aged 7-64 years with a confirmed diagnosis of NPC were enrolled. 32 patients were included in the primary modified intention-to-treat analysis. NALL met the CI-CS primary endpoint (mean difference 0.86, SD = 2.52, 90% CI 0.25, 1.75, p = 0.029), as well as secondary endpoints. No treatment-related serious adverse events occurred.

Conclusions: NALL demonstrated a statistically significant and clinical meaningfully improvement in symptoms, functioning, and quality of life in 6 weeks, the clinical effect of which was lost after the 6-week washout period. NALL was safe and well-tolerated, informing a favorable benefit-risk profile for the treatment of NPC. CLINICALTRIALS.

Gov identifier: NCT03759639.

Keywords: Acetyl-leucine; Ataxia; Lysosomal storage disorder; Niemann–Pick disease type C; Symptomatic therapy.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Double-Blind Method
  • Humans
  • Leucine / analogs & derivatives
  • Leucine / therapeutic use
  • Middle Aged
  • Niemann-Pick Disease, Type C* / diagnosis
  • Niemann-Pick Disease, Type C* / drug therapy
  • Quality of Life
  • Treatment Outcome
  • Young Adult


  • Leucine
  • acetylleucine

Associated data

  • ClinicalTrials.gov/NCT03759639