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

Yoon Myung Kim, Mi Sun Yum, Sun Hee Heo, Taeho Kim, Hee Kyung Jin, Jae Sung Bae, Go Hun Seo, Arum Oh, Hee Mang Yoon, Hyun Taek Lim, Hyo Won Kim, Tae Sung Ko, Hyeong Seok Lim, Mark J. Osborn, Jakub Tolar, Claudia Cozma, Arndt Rolfs, Ari Zimran, Beom Hee Lee, Han Wook Yoo

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)124-131
Number of pages8
JournalJournal of medical genetics
Issue number2
StatePublished - Feb 1 2020


  • Metabolic disorders
  • Neurology
  • Parkinson's disease

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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