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

Tatiana Bremova-Ertl, Jens Claassen, Tomas Foltan, Jordi Gascon-Bayarri, Paul Gissen, Andreas Hahn, Anhar Hassan, Anita Hennig, Simon A. Jones, Miriam Kolnikova, Kyriakos Martakis, Jan Raethjen, Uma Ramaswami, Reena Sharma, Susanne A. Schneider

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)1651-1662
Number of pages12
JournalJournal of Neurology
Issue number3
StatePublished - Mar 2022


  • Acetyl-leucine
  • Ataxia
  • Lysosomal storage disorder
  • Niemann–Pick disease type C
  • Symptomatic therapy

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


Dive into the research topics of 'Efficacy and safety of N-acetyl-l-leucine in Niemann–Pick disease type C'. Together they form a unique fingerprint.

Cite this