Pilot study using ambroxol as a pharmacological chaperone in type 1 Gaucher disease

Blood Cells Mol Dis. 2013 Feb;50(2):134-7. doi: 10.1016/j.bcmd.2012.09.006. Epub 2012 Oct 22.


The purpose of this pilot was to assess the tolerability and efficacy of ambroxol as a pharmacological chaperone in patients with symptomatic, type 1 Gaucher disease who present with measurable disease parameters but are not receiving enzyme replacement therapy (ERT) in order to provide proof of concept and/or ascertain the suitability of ambroxol for a larger clinical trial. The Israeli Ministry of Health Form 29c was employed to prescribe ambroxol for off-label use. Twelve patients were dispensed 2 capsules of 75 mg of ambroxol daily for 6 months. There were 8 females (66.7%). Mean age at entry was 41.1 (range: 24-63) years. Mean body weight at entry was 66.4 (range: 46.5-100) kg. One patient withdrew because of a hypersensitivity reaction, one because of elective splenectomy. No patient experienced clinically relevant deterioration in disease parameters measured. One patient achieved a robust response relative to baseline: +16.2% hemoglobin; +32.9% platelets; -2.8% liver volume; and -14.4% spleen volume. Three patients, including the above one, elected to continue on ambroxol for a further 6 months: hemoglobin levels and liver volumes were relatively stable, but platelet counts further increased in the above patient (+52.6% from baseline) and spleen volumes decreased further in all three patients (-6.4%, -18.6%, and -23.4% from baseline). Thus, ambroxol may be a safe option for Gaucher disease patients with potential disease-specific efficacy and should be expanded into a clinical trial using higher doses and placebo-controlled design.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Ambroxol / administration & dosage
  • Ambroxol / adverse effects
  • Ambroxol / pharmacology
  • Ambroxol / therapeutic use*
  • Drug Hypersensitivity
  • Enzyme Stability / drug effects
  • Female
  • Gaucher Disease / drug therapy*
  • Gaucher Disease / pathology
  • Gaucher Disease / surgery
  • Glucosylceramidase / chemistry
  • Glucosylceramidase / drug effects
  • Hexosaminidases / metabolism
  • Humans
  • Liver / pathology
  • Male
  • Middle Aged
  • Off-Label Use
  • Organ Size / drug effects
  • Pilot Projects
  • Platelet Count
  • Spleen / pathology
  • Splenectomy
  • Treatment Outcome
  • Young Adult


  • Ambroxol
  • Hexosaminidases
  • chitotriosidase
  • Glucosylceramidase