title: Pilot study using ambroxol as a pharmacological chaperone in type 1 Gaucher disease.
abstract: 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.
authors.affiliation: Gaucher Clinic, Shaare Zedek Medical Center, Hadassah Medical School, Hebrew University, Jerusalem, Israel.
authors.forename: Ari
authors.initials: A
authors.lastname: Zimran
authors.forename: Gheona
authors.initials: G
authors.lastname: Altarescu
authors.forename: Deborah
authors.initials: D
authors.lastname: Elstein
mesh_terms: D000328:Adult; D000551:Ambroxol / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004342:Drug Hypersensitivity; D004795:Enzyme Stability / Q000187:drug effects; D005260:Female; D005776:Gaucher Disease / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D005962:Glucosylceramidase / Q000737:chemistry / Q000187:drug effects; D006596:Hexosaminidases / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D056687:Off-Label Use; D009929:Organ Size / Q000187:drug effects; D010865:Pilot Projects; D010976:Platelet Count; D013154:Spleen / Q000473:pathology; D013156:Splenectomy; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000551:Ambroxol; D006596:Hexosaminidases; C086400:chitotriosidase; D005962:Glucosylceramidase