{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:03:14Z","timestamp":1790532194647,"version":"4.1.0"},"reference-count":35,"publisher":"American Medical Association (AMA)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"<jats:sec id=\"ab-zoi230588-4\"><jats:title>Importance<\/jats:title><jats:p>Ambroxol was identified as an enhancer of stability and residual activity of several misfolded glucocerebrosidase variants in 2009.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi230588-5\"><jats:title>Objectives<\/jats:title><jats:p>To assess hematologic and visceral outcomes, biomarker changes, and safety of ambroxol therapy for patients with Gaucher disease (GD) without disease-specific treatment.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi230588-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>Patients with GD who could not afford enzyme replacement therapy were enrolled and received oral ambroxol from May 6, 2015, to November 9, 2022, at Xinhua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China. Thirty-two patients with GD (29 with GD type 1, 2 with GD type 3, and 1 with GD intermediate types 2-3) were enrolled. Of those, 28 patients were followed up for longer than 6 months; 4 were excluded due to loss of follow-up. Data analyses were performed from May 2015 to November 2022.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi230588-7\"><jats:title>Intervention<\/jats:title><jats:p>An escalating dose of oral ambroxol (mean [SD] dose, 12.7 [3.9] mg\/kg\/d).<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi230588-8\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>Patients with GD receiving ambroxol were followed up in a genetic metabolism center. Biomarkers of chitotriosidase activity and glucosylsphingosine level, liver and spleen volumes, and hematologic parameters were measured at baseline and various time points throughout the ambroxol treatment.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi230588-9\"><jats:title>Results<\/jats:title><jats:p>A total of 28 patients (mean [SD] age, 16.9 [15.3] years; 15 male patients [53.6%]) received ambroxol for a mean (SD) duration of 2.6 (1.7) years. Two patients with severe symptoms at baseline experienced deterioration of hematologic parameters and biomarkers and were deemed nonresponders; clinical response was observed in the other 26 patients. After 2.6 years of ambroxol treatment, the mean (SD) hemoglobin concentration improved from 10.4 (1.7) to 11.9 (1.7) g\/dL (mean [SD], 1.6 [1.7] g\/dL; 95% CI, 0.8-2.3 g\/dL; <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001), and the mean (SD) platelet count improved from 69 (25) to 78 (30)\u2009\u00d7\u200910<jats:sup>3<\/jats:sup>\/\u00b5L (mean [SD], 9 [22]\u2009\u00d7\u200910<jats:sup>3<\/jats:sup>\/\u00b5L; 95% CI, \u22122 to 19\u2009\u00d7\u200910<jats:sup>3<\/jats:sup>\/\u00b5L; <jats:italic>P<\/jats:italic>\u2009=\u2009.09). The mean (SD) spleen volume decreased from 17.47 (7.18) to 12.31 (4.71) multiples of normal (MN) (mean [SD], \u22125.16 [5.44] MN; 95% CI, \u221210.19 to \u22120.13; <jats:italic>P<\/jats:italic>\u2009=\u2009.04), and the mean (SD) liver volume decreased from 1.90 (0.44) to 1.50 (0.53) MN (mean [SD], \u22120.39 [0.42] MN; 95% CI, \u22120.75 to \u22120.04; <jats:italic>P<\/jats:italic>\u2009=\u2009.03). Biomarker median percentage changes from baseline were \u221243.1% for chitotriosidase activity (from 14\u202f598 [range, 3849-29\u202f628] to 8312 [range, 1831-16\u202f842] nmol\/mL\/h; <jats:italic>z<\/jats:italic>\u2009=\u2009\u22123.413; <jats:italic>P<\/jats:italic>\u2009=\u2009.001) and \u221234.1% for glucosylsphingosine level (from 251.3 [range, 73.6-944.2] to 165.7 [range, 21.3-764.8] ng\/mL; <jats:italic>z<\/jats:italic>\u2009=\u2009\u22122.756; <jats:italic>P<\/jats:italic>\u2009=\u2009.006). Patients were divided into subgroups according to age when initiating treatment; those who received treatment at a younger age (mean [SD] age, 6.3 [2.7] years) experienced more rapid improvements: hemoglobin concentration increased by 16.5% (from 10.3 [1.5] to 12.0 [1.5] g\/dL; mean [SD] change, 1.6 [1.6] g\/dL; 95% CI, 0.7-2.5 g\/dL; <jats:italic>P<\/jats:italic>\u2009=\u2009.002), and platelet count increased by 12.0% (from 75 [24] to 84 [33]\u2009\u00d7\u200910<jats:sup>3<\/jats:sup>\/\u00b5L; mean [SD] change, 9 [26]\u2009\u00d7\u200910<jats:sup>3<\/jats:sup>\/\u00b5L; 95% CI, \u22125 to 24\u2009\u00d7\u200910<jats:sup>3<\/jats:sup>\/\u00b5L; <jats:italic>P<\/jats:italic>\u2009=\u2009.17); whereas chitotriosidase activity decreased by 64.0% (from 15\u202f710 [range, 4092-28\u202f422] to 5658 [range, 1146-16\u202f843] nmol\/mL\/h; <jats:italic>z<\/jats:italic>\u2009=\u2009\u22122.803; <jats:italic>P<\/jats:italic>\u2009=\u2009.005), and glucosylsphingosine level decreased by 47.3% (from 248.5 [range, 122.8-674.9] to 131.0 [range, 41.1-448.5] ng\/mL; <jats:italic>z<\/jats:italic>\u2009=\u2009\u22122.385; <jats:italic>P<\/jats:italic>\u2009=\u2009.02). Three of the 28 patients experienced mild and transient adverse events.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi230588-10\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>In this case series of ambroxol repurposing among patients with GD, long-term treatment with ambroxol was safe and associated with patient improvement. Improvements in hematologic parameters, visceral volumes, and plasma biomarkers were larger among patients with relatively mild symptoms of GD and patients who received initial treatment at younger ages.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2023.19364","type":"journal-article","created":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T18:19:07Z","timestamp":1687371547000},"page":"e2319364","source":"Crossref","is-referenced-by-count":25,"title":["Use of Ambroxol as Therapy for Gaucher Disease"],"prefix":"10.1001","volume":"6","author":[{"given":"Xia","family":"Zhan","sequence":"first","affiliation":[{"name":"Department of Pediatric Endocrinology and Genetics, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Genetics, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo H. B.","family":"Maegawa","sequence":"additional","affiliation":[{"name":"Vagelos College of Physicians and Surgeons, Columbia University, Department of Pediatrics, Columbia University Medical Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Genetics, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Genetics, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dengbin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinning","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2023,6,21]]},"reference":[{"key":"zoi230588r1","doi-asserted-by":"publisher","first-page":"S2","DOI":"10.1016\/j.ejim.2006.07.005","article-title":"Epidemiology and natural history of Gaucher\u2019s disease.","volume":"17","author":"Mehta","year":"2006","journal-title":"Eur J Intern Med"},{"issue":"8","key":"zoi230588r2","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1038\/jhg.2017.36","article-title":"Successful newborn screening for Gaucher disease using fluorometric assay in 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