{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:03:20Z","timestamp":1790532200093,"version":"4.1.0"},"reference-count":26,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100023181","name":"Medical Research Agency","doi-asserted-by":"crossref","award":["2021\/ABM\/02\/00014"],"award-info":[{"award-number":["2021\/ABM\/02\/00014"]}],"id":[{"id":"10.13039\/501100023181","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Gaucher disease (GD) is a lysosomal storage disorder caused by deficiency of \u03b2-glucocerebrosidase, leading to accumulation of glucocerebroside in lysosomes. Type 1 GD is most commonly associated with the N370S mutation and lacks neurological involvement, whereas the neuronopathic forms (types 2 and 3), frequently linked to L444P homozygosity, present with progressive neurological symptoms. Enzyme replacement therapy (ERT) effectively treats visceral manifestations but does not cross the blood\u2013brain barrier and, therefore, does not improve neurological outcomes. Ambroxol, a plant-derived mucolytic agent, has been shown to act as a pharmacological chaperone capable of increasing residual enzyme activity and crossing into the central nervous system, with reports suggesting neurological benefit in L444P homozygotes. Methods: We evaluated 13 patients with type 3 GD (L444P\/L444P homozygotes) who received ambroxol at 10 mg\/kg\/day for one year as part of a clinical trial. All participants had been on long-term ERT with stable biomarker levels (chitotriosidase, glucosylsphingosine [Lyso-GL1]) and hematological parameters. Neurological symptoms were assessed using the modified Severity Scoring Tool (mSST). Biomarkers and hematologic indices were monitored throughout the study. Results: Ambroxol treatment resulted in a reduction in severity or complete resolution of selected neurological symptoms in several patients. Conclusions: In patients with type 3 GD receiving stable ERT, ambroxol demonstrated beneficial effects on neurological symptom expression. Some improvement was observed in biomarkers; the activity of chitotrosidase and concentration of lyso-Gl1 decreased. These findings support the therapeutic potential of ambroxol as an adjunctive treatment for neuronopathic Gaucher disease.<\/jats:p>","DOI":"10.3390\/life16030485","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:13:14Z","timestamp":1773659594000},"page":"485","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Safety and Efficacy of Ambroxol Therapy in Polish Patients with Gaucher Disease"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1849-8375","authenticated-orcid":false,"given":"Patryk","family":"Lipi\u0144ski","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Medical Center of Postgraduate Education, 01-813 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9736-2838","authenticated-orcid":false,"given":"Dariusz","family":"Rokicki","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Nutrition and Metabolic Diseases, The Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8053-8959","authenticated-orcid":false,"given":"Karolina","family":"Chwia\u0142kowska","sequence":"additional","affiliation":[{"name":"Laboratory of Computational Molecular Medicine, Clinical Research Centre, Medical University of Bia\u0142ystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3729-0518","authenticated-orcid":false,"given":"Micha\u0142","family":"Ciborowski","sequence":"additional","affiliation":[{"name":"Metabolomics and Proteomics Laboratory, Clinical Research Centre, Medical University of Bia\u0142ystok, 15-089 Bia\u0142ystok, Poland"},{"name":"Department of Medical Biochemistry, Medical University of Bia\u0142ystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9477-057X","authenticated-orcid":false,"given":"Joanna","family":"Godzie\u0144","sequence":"additional","affiliation":[{"name":"Metabolomics and Proteomics Laboratory, Clinical Research Centre, Medical University of Bia\u0142ystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9814-0324","authenticated-orcid":false,"given":"Aleksandra","family":"Jezela-Stanek","sequence":"additional","affiliation":[{"name":"Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 01-138 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1779-8368","authenticated-orcid":false,"given":"Urszula","family":"Korotko","sequence":"additional","affiliation":[{"name":"Centre for Digital Medicine, Medical University of Bia\u0142ystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miros\u0142aw","family":"Kwa\u015bniewski","sequence":"additional","affiliation":[{"name":"Centre for Bioinformatics and Data Analysis, Medical University of Bia\u0142ystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0701-4961","authenticated-orcid":false,"given":"Magdalena","family":"Niemira","sequence":"additional","affiliation":[{"name":"Laboratory of Genomics and Epigenetic Analysis, Clinical Research Centre, Medical University of Bia\u0142ystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Szyma\u0144ska-Ro\u017cek","sequence":"additional","affiliation":[{"name":"Faculty of Mathematics, Informatics and Mechanics, University of Warsaw, 00-927 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8872-6476","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Syczewska","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, The Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8935-1768","authenticated-orcid":false,"given":"Anna","family":"Tylki-Szyma\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Nutrition and Metabolic Diseases, The Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Stirnemann, J., Belmatoug, N., Camou, F., Serratrice, C., Froissart, R., Caillaud, C., Levade, T., Astudillo, L., Serratrice, J., and Brassier, A. (2017). A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18020441"},{"key":"ref_2","unstructured":"Adam, M.P., Bick, S., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. (1993). Gaucher Disease. GeneReviews\u00ae, University of Washington."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1002\/jimd.12235","article-title":"The definition of neuronopathic Gaucher disease","volume":"43","author":"Schiffmann","year":"2020","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Istaiti, M., Yahalom, G., Cohen, M., Skrahina, V., Skrahin, A., Lukas, J., Rolfs, A., and Zimran, A. (2025). Sidransky Syndrome-GBA1-Related Parkinson\u2019s Disease and Its Targeted Therapies. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26073435"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1186\/s13023-025-03654-y","article-title":"Gaucher disease type 3 from infancy through adulthood: A conceptual model of signs, symptoms, and impacts associated with ataxia and cognitive impairment","volume":"20","author":"Schiffmann","year":"2025","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.ymgme.2016.12.001","article-title":"Long-term hematological, visceral, and growth outcomes in children with Gaucher disease type 3 treated with imiglucerase in the International Collaborative Gaucher Group Gaucher Registry","volume":"120","author":"Vellodi","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1002\/acn3.292","article-title":"Ambroxol chaperone therapy for neuronopathic Gaucher disease: A pilot study","volume":"3","author":"Narita","year":"2016","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_8","first-page":"3750","article-title":"Individualized screening for chaperone activity in Gaucher disease using multiple patient derived primary cell lines","volume":"10","author":"Ivanova","year":"2018","journal-title":"Am. J. Transl. Res."},{"key":"ref_9","first-page":"100476","article-title":"Effect of Ambroxol chaperone therapy on Glucosylsphingosine (Lyso-Gb1) levels in two Canadian patients with type 3 Gaucher disease","volume":"20","author":"Charkhand","year":"2019","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_10","first-page":"100678","article-title":"In vitro and in vivo effects of Ambroxol chaperone therapy in two Italian patients affected by neuronopathic Gaucher disease and epilepsy","volume":"25","author":"Ciana","year":"2020","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.ejpn.2021.03.013","article-title":"Early initiation of ambroxol treatment diminishes neurological manifestations of type 3 Gaucher disease: A long-term outcome of two siblings","volume":"32","author":"Ramadza","year":"2021","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1001\/jamaneurol.2019.4611","article-title":"Ambroxol for the Treatment of Patients With Parkinson Disease With and Without Glucocerebrosidase Gene Mutations: A Nonrandomized, Noncontrolled Trial","volume":"77","author":"Mullin","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.parkreldis.2021.02.003","article-title":"Ambroxol increases glucocerebrosidase (GCase) activity and restores GCase translocation in primary patient-derived macrophages in Gaucher disease and Parkinsonism","volume":"84","author":"Kopytova","year":"2021","journal-title":"Park. Relat. Disord."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1651-2227.1986.tb14936.x","article-title":"Gaucher disease\u2014Norrbottnian type (III). Neuropaediatric and neurobiological aspects of clinical patterns and treatment","volume":"326","author":"Erikson","year":"1986","journal-title":"Acta Paediatr. Scand. Suppl."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1097\/01.gim.0000196443.42899.25","article-title":"Characterization of neuronopathic Gaucher disease among ethnic Poles","volume":"8","author":"Keddache","year":"2006","journal-title":"Genet. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1007\/s10545-007-0595-x","article-title":"A severity scoring tool to assess the neurological features of neuronopathic Gaucher disease","volume":"30","author":"Davies","year":"2007","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1007\/s10545-011-9347-z","article-title":"Four-year follow-up of chronic neuronopathic Gaucher disease in Europeans using a modified severity scoring tool","volume":"34","author":"Davies","year":"2011","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1172\/JCI117084","article-title":"Marked elevation of plasma chitotriosidase activity. A novel hallmark of Gaucher disease","volume":"93","author":"Hollak","year":"1994","journal-title":"J. Clin. Investig."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Boer, D.E.C., van Smeden, J., Bouwstra, J.A., and Aerts, J. (2020). Glucocerebrosidase: Functions in and Beyond the Lysosome. J. Clin. Med., 9.","DOI":"10.3390\/jcm9030736"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e118","DOI":"10.1182\/blood-2011-05-352971","article-title":"Elevated plasma glucosylsphingosine in Gaucher disease: Relation to phenotype, storage cell markers, and therapeutic response","volume":"118","author":"Dekker","year":"2011","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Cozma, C., Cullufi, P., Kramp, G., Hovakimyan, M., Velmishi, V., Gjikopulli, A., Tomori, S., Fischer, S., Oppermann, S., and Grittner, U. (2020). Treatment Efficiency in Gaucher Patients Can Reliably Be Monitored by Quantification of Lyso-Gb1 Concentrations in Dried Blood Spots. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134577"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.ymgme.2018.02.004","article-title":"Plasma chitotriosidase activity versus plasma glucosylsphingosine in wide spectrum of Gaucher disease phenotypes\u2014A statistical insight","volume":"123","author":"Hasinski","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mohamed, F.E., and Al-Jasmi, F. (2024). Exploring the efficacy and safety of Ambroxol in Gaucher disease: An overview of clinical studies. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1335058"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Istaiti, M., Frydman, D., Dinur, T., Szer, J., Revel-Vilk, S., and Zimran, A. (2023). High-Dose Ambroxol Therapy in Type 1 Gaucher Disease Focusing on Patients with Poor Response to Enzyme Replacement Therapy or Substrate Reduction Therapy. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076732"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e2319364","DOI":"10.1001\/jamanetworkopen.2023.19364","article-title":"Use of Ambroxol as Therapy for Gaucher Disease","volume":"6","author":"Zhan","year":"2023","journal-title":"JAMA Netw. Open"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.bcmd.2012.09.006","article-title":"Pilot study using ambroxol as a pharmacological chaperone in type 1 Gaucher disease","volume":"50","author":"Zimran","year":"2013","journal-title":"Blood Cells Mol. Dis."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/3\/485\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T05:54:45Z","timestamp":1773813285000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/3\/485"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,16]]},"references-count":26,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["life16030485"],"URL":"https:\/\/doi.org\/10.3390\/life16030485","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,16]]}}}