High-Dose Ambroxol Therapy in Type 1 Gaucher Disease Focusing on Patients with Poor Response to Enzyme Replacement Therapy or Substrate Reduction Therapy

Istaiti, M; Frydman, D; Dinur, T; Szer, J; Revel-Vilk, S; Zimran, A

Author(s): Istaiti, M; Frydman, D; Dinur, T; Szer, J; Revel-Vilk, S; Zimran, A;
Details: Publication Year 2023-04-04,Volume 24,Issue #7,Page 6732
Journal Title: International Journal of Molecular Sciences
Publication Type: Research article
Abstract: Ambroxol hydrochloride (ABX), an oral mucolytic drug available over the counter for many years, acts as a pharmacological chaperone for mutant glucocerebrosidase, albeit at higher doses. Proof-of-concept reports have been published over the past decade on all three types of Gaucher disease (GD). Here, we assess the safety and efficacy of 12 months of 600 mg ambroxol per day in three groups of Type 1 GD patients with a suboptimal response to enzyme replacement therapy (ERT) or substrate reduction therapy (SRT), defined as platelet count < 100 x 10(3)/L, lumbar spine bone density T-score < -2.0, and/or LysoGb1 > 200 ng/mL, and for a group of naive patients who had abnormal values in two of these three parameters. We enrolled 40 patients: 28 ERT- or SRT-treated, and 12 naive. There were no severe adverse effects (AEs). There were 24 dropouts, mostly due to AEs (n = 12), all transient, and COVID-19 (n = 7). Among the 16 completers, 5 (31.2%) had a >20% increase in platelet count, 6 (37.5%) had a >0.2 increase in T-score, and 3 (18.7%) had a >20% decrease in Lyso-Gb1. This study expands the number of patients exposed to high-dose ABX, showing good safety and satisfactory efficacy, and provides an additional rationale for adding off-label ABX to the arsenal of therapies that could be offered to patients with GD1 and a suboptimal response or those unable to receive ERT or SRT.
Publisher: MDPI
Keywords: Humans; *Gaucher Disease/drug therapy; *Ambroxol/therapeutic use; Enzyme Replacement Therapy; *covid-19; Lumbar Vertebrae; Gaucher disease (GD); Lyso-Gb1; ambroxol; chaperone therapy; enzyme replacement therapy (ERT); suboptimal response; substrate reduction therapy (SRT)
Department(s): Clinical Haematology
PubMed ID: 37047707
Publisher's Version: https://doi.org/10.3390/ijms24076732
Open Access at Publisher's Site: https://doi.org/10.3390/ijms24076732
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-07-25 05:27:37

Last Modified: 2023-07-25 05:28:06