Pharmacologic properties of high-dose ambroxol in four patients with Gaucher disease and myoclonic epilepsy

J Med Genet. 2020 Feb;57(2):124-131. doi: 10.1136/jmedgenet-2019-106132. Epub 2019 Oct 24.


Background: Ambroxol (ABX) has been suggested as an augmentative pharmacological agent for neuronopathic Gaucher disease (nGD). This study assessed the long-term safety and efficacy of combined therapy with high-dose ABX and enzyme replacement therapy (ERT) in nGD.

Methods: ABX+ERT therapy was administered for 4.5 years in four patients with nGD. ABX was initiated at a dose of 1.5 mg/kg/day, and the dose was escalated up to 27 mg/kg/day. The target plasma level was 10 µmol/L or less. The changes in glucocerebrosidase activity, biochemical, safety and neurocognitive findings were assessed.

Results: Enhanced residual GCcase activity was observed in all patients, as evidenced in both in vitro and in vivo studies. During the first 2 years of study with ABX (up to 21 mg/kg/day), mean seizure frequencies and neurocognitive function worsened. After ABX dosage was increased up to 27 mg/kg/day of ABX, its trough plasma concentration was 3.2-8.8 µmol/L. Drug-to-drug interaction, especially with antiepileptic drug significantly affected the pharmacokinetic parameters of ABX. Importantly, at 27 mg/kg/day of ABX, the seizure frequencies markedly decreased from the baseline, and the neurocognitive function was improved. In addition, Lyso-Gb1, a biomarker for the severity and progression of GD, was normalised in all patients. High-dose ABX was well-tolerated with no severe adverse events.

Conclusions: Long-term treatment with high-dose ABX+ERT was safe and might help to arrest the progression of the neurological manifestations in GD.

Keywords: Parkinson's disease; metabolic disorders; neurology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Ambroxol / administration & dosage*
  • Biomarkers / blood
  • Child
  • Dose-Response Relationship, Drug
  • Enzyme Replacement Therapy*
  • Epilepsies, Myoclonic / blood
  • Epilepsies, Myoclonic / drug therapy*
  • Epilepsies, Myoclonic / pathology
  • Female
  • Gaucher Disease / blood
  • Gaucher Disease / drug therapy*
  • Gaucher Disease / pathology
  • Glucosylceramidase / blood
  • Humans
  • Male


  • Biomarkers
  • Ambroxol
  • Glucosylceramidase