Ambroxol in Gaucher disease and GBA1-related Parkinson disease: an updated systematic review.

BACKGROUND: Ambroxol (ABX) is a central nervous system (CNS)-penetrant compound that can increase glucocerebrosidase activity and has been investigated in Gaucher disease (GD) and GBA1-related Parkinson disease (GBA1-PD). METHODS: This PRISMA 2020 systematic review and narrative synthesis searched PubMed/MEDLINE, Europe PMC, SSRN and ClinicalTrials.gov through 19 August 2026, with an additional Web of Science Core Collection search performed during revision on 14 September 2026, without restrictions on date, language or publication status. Two reviewers independently selected studies, extracted data and assessed risk of bias using design-specific tools. Substantial clinical and methodological heterogeneity precluded meta-analysis RESULTS: Of 149 records in the original searches, 137 were screened, 41 full texts were assessed and 20 clinical outcome reports were included. The additional Web of Science search retrieved 50 records and did not identify further clinical outcome reports. Evidence in GD consisted mainly of small, uncontrolled and sometimes overlapping reports. Biochemical and neurological improvements were described in selected patients, but outcome definitions and functional responses varied. In GBA1-PD, conclusions remain provisional because the AMBITIOUS results are available only as a non-peer-reviewed preprint and did not show disease modification. Evidence on the safety of chronic high-dose treatment is limited. CONCLUSIONS: Biomarker changes alone do not establish clinical efficacy. ABX remains an off-label, investigational treatment in GD and GBA1-PD, and no GBA1 genotype or functional assay currently defines a validated indication.