Therapeutic Interventions in Niemann-Pick Disease Type C: A Systematic Review of Clinical Outcomes and Safety

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• Picked for Biochemistry (medical) (paper of the day, 28 October 2026): Niemann-Pick lipid trafficking and cholesterol biomarkers address metabolic disease

Abstract

Background: Niemann-Pick disease type C (NPC) is a rare, progressive lysosomal storage disorder characterized by impaired intracellular lipid trafficking, leading to systemic, neurological, and psychiatric manifestations. Although supportive care was historically the main treatment approach, several disease-modifying and symptomatic therapies have recently emerged. This systematic review aimed to evaluate the efficacy and safety of current therapeutic strategies for NPC. Methods: A systematic literature search was conducted in PubMed, Scopus, and ClinicalTrials.gov from inception to 1 August 2026. Eligible studies included randomized controlled trials and interventional clinical studies involving patients with NPC of any age or sex. Interventions included miglustat, arimoclomol, N-acetyl-L-leucine (NALL), hydroxypropyl-β-cyclodextrin (HPβCD), vorinostat, N-acetylcysteine (NAC), efavirenz, nizubaglustat and other therapeutic strategies. Outcomes included neurological progression, clinical severity scores, ataxia measures, quality of life, biomarkers, cognition, and adverse events. Due to heterogeneity in study designs and outcome measures, findings were synthesized narratively. Results: Twenty-four studies representing approximately 475 participants, after removal of documented cohort overlap, were included. Miglustat showed evidence of neurological stabilization, particularly when initiated early, with mainly gastrointestinal adverse effects. Arimoclomol demonstrated evidence of slowing neurological progression and was generally well tolerated, although longer-term safety and effectiveness data remain necessary. NALL improved ataxia-related symptoms and was generally well tolerated. HPβCD demonstrated biological target engagement, including changes in cholesterol-related biomarkers, but clinical findings were mixed: uncontrolled intrathecal and intravenous studies suggested stabilization or improvement, whereas controlled evidence was less supportive. Hearing impairment remained an important safety concern. Evidence for vorinostat, NAC, efavirenz, and nizubaglustat was limited by small samples and early-phase or uncontrolled designs. Conclusions: The available evidence most consistently supports miglustat, arimoclomol, and NALL for stabilizing neurological progression or improving functional outcomes in NPC. However, differences in study design, outcome measures, and follow-up preclude direct comparison between therapies. HPβCD remains investigational because its biological activity has not translated into consistent controlled clinical benefit and requires careful safety monitoring. Larger controlled studies using standardized clinical outcomes and reliable biomarkers are needed to define long-term effectiveness and optimize treatment selection.

Abstract as published, via PubMed.