Safety and Efficacy of Ambroxol Therapy in Polish Patients with Gaucher Disease

Background: Gaucher disease (GD) is a lysosomal storage disorder caused by deficiency of β-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–brain 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.