Upgrading the evidence for the use of ambroxol in Gaucher disease and GBA related Parkinson: Investigator initiated registry based on real life data.

Abstract

Ambroxol hydrochloride is an oral mucolytic drug available over-the-counter for many years as cough medicine. In 2009 it was identified as a pharmacological chaperone for mutant glucocerebrosidase, albeit in a several-fold higher dose. Unfortunately, there have been no pharma-driven clinical trials to establish its use. Thus, real-world observational data are needed on the safety and efficacy of ambroxol for patients with Gaucher disease (GD) and GBA-Parkinson disease (GBA-PD). Clinicians treating patients with ambroxol for GD and GBA-PD were approached to collaborate in an investigator-initiated registry. Anonymized data were collected, including demographics, GD type, GD-specific therapy (when applicable), adverse events (AEs), and, when available, efficacy data. We report the data of the first 41 patients (25 females) at a median (range) age 17 (1.5-74) from 13 centers; 11 with GD type 1(four diagnosed with PD), 27 with neuronopathic GD (nGD), and three GBA mutation carriers with PD. The median (range) treatment period and maximum dose of ambroxol were 19 (1-76) months and 435 (75-1485) mg/day, respectively. One patient with type 2 GD died of her disease. No other severe AEs were reported. Twelve patients experienced AE, including minor bowel discomfort, cough, allergic reaction, mild proteinuria, dizziness and disease progression. Clinical benefits were reported in 25 patients, including stable or improved neurological status, increased physical activity, and reduced fatigue. Until the approval of specific therapies for nGD and disease-modification for GBA-PD, these preliminary data may be encouraging to physicians and patients who consider an off-label use of ambroxol.

• Authors: Majdolen Istaiti, Shoshana Revel-Vilk, Michal Becker-Cohen, Tama Dinur, Uma Ramaswami, Daniela Castillo-Garcia, Magdalena Ceron-Rodriguez, Alicia Chan, Predrag Rodic, Radka Stefanova Tincheva, Walla Al-Hertani, Beom Hee Lee, Chia-Feng Yang, Beata Kiec-Wilk, Agata Fiumara, Barbara Rubio, Ari Zimran
• Journal: American journal of hematology (Am J Hematol) Vol. 96 Issue 5 Pg. 545-551 (05 01 2021) ISSN: 1096-8652 [Electronic] United States
• PMID: 33606887 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 Wiley Periodicals LLC.

Chemical References

• Ambroxol
• Glucosylceramidase

Topics

• Adolescent
• Adult
• Aged
• Ambroxol (adverse effects, pharmacology, therapeutic use)
• Biological Availability
• Blood-Brain Barrier
• Child
• Child, Preschool
• Combined Modality Therapy
• Enzyme Replacement Therapy
• Female
• Gaucher Disease (drug therapy)
• Glucosylceramidase (deficiency, genetics, metabolism, therapeutic use)
• Humans
• Infant
• Male
• Middle Aged
• Off-Label Use
• Parkinson Disease (drug therapy, genetics)
• Protein Stability (drug effects)
• Registries
• Young Adult