PMID- 37047707
OWN - NLM
STAT- MEDLINE
DCOM- 20230414
LR  - 20230415
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 7
DP  - 2023 Apr 4
TI  - High-Dose Ambroxol Therapy in Type 1 Gaucher Disease Focusing on Patients with 
      Poor Response to Enzyme Replacement Therapy or Substrate Reduction Therapy.
LID - 10.3390/ijms24076732 [doi]
LID - 6732
AB  - 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.
FAU - Istaiti, Majdolen
AU  - Istaiti M
AUID- ORCID: 0000-0001-7598-2828
AD  - Gaucher Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel.
FAU - Frydman, Dafna
AU  - Frydman D
AD  - Gaucher Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel.
FAU - Dinur, Tama
AU  - Dinur T
AD  - Gaucher Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel.
FAU - Szer, Jeff
AU  - Szer J
AUID- ORCID: 0000-0001-6783-2301
AD  - Peter MacCallum Center, Royal Melbourne Hospital, Department of Medicine, 
      University of Melbourne, Melbourne, VIC 3050, Australia.
FAU - Revel-Vilk, Shoshana
AU  - Revel-Vilk S
AUID- ORCID: 0000-0001-9151-0337
AD  - Gaucher Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel.
AD  - Faculty of Medicine, Hebrew University, Jerusalem 91120, Israel.
FAU - Zimran, Ari
AU  - Zimran A
AUID- ORCID: 0000-0003-0077-8608
AD  - Gaucher Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel.
AD  - Faculty of Medicine, Hebrew University, Jerusalem 91120, Israel.
LA  - eng
GR  - IISR-2017-104260/Takeda (Japan)/
PT  - Journal Article
DEP - 20230404
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 200168S0CL (Ambroxol)
SB  - IM
MH  - Humans
MH  - *Gaucher Disease/drug therapy
MH  - *Ambroxol/therapeutic use
MH  - Enzyme Replacement Therapy
MH  - *COVID-19
MH  - Lumbar Vertebrae
PMC - PMC10095311
OTO - NOTNLM
OT  - Gaucher disease (GD)
OT  - Lyso-Gb1
OT  - ambroxol
OT  - chaperone therapy
OT  - enzyme replacement therapy (ERT)
OT  - suboptimal response
OT  - substrate reduction therapy (SRT)
COIS- The Gaucher unit receives support from Sanofi/Genzyme for participation in the 
      ICGG registry from Takeda-for GOS and Pfizer for TALIAS, and research grants from 
      Shire (now Takeda), Pfizer, Sanofi/Genzyme, and Centogene. M.I., D.F., and T.D., 
      no conflicts to declare. J.S. received honoraria and consultancy fees from 
      Takeda, Alexion, Arrowhead, Eli Lilly, Kira, Novartis, Sobi, and Samsung Bioepis. 
      S.R.-V. received research grants, speaker fees, travel support, and advisory fee 
      from Pfizer, Sanofi Genzyme, and Takeda. A.Z. received honoraria from Takeda, 
      Pfizer, and BioEvents, and consulting fees from Prevail Therapeutics and Takeda.
EDAT- 2023/04/14 06:00
MHDA- 2023/04/14 06:42
PMCR- 2023/04/04
CRDT- 2023/04/13 01:14
PHST- 2023/03/14 00:00 [received]
PHST- 2023/03/27 00:00 [revised]
PHST- 2023/04/03 00:00 [accepted]
PHST- 2023/04/14 06:42 [medline]
PHST- 2023/04/13 01:14 [entrez]
PHST- 2023/04/14 06:00 [pubmed]
PHST- 2023/04/04 00:00 [pmc-release]
AID - ijms24076732 [pii]
AID - ijms-24-06732 [pii]
AID - 10.3390/ijms24076732 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Apr 4;24(7):6732. doi: 10.3390/ijms24076732.