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Significant improvements seen in hematologic parameters, visceral volumes, and plasma biomarkers in patients with Gaucher disease, suggesting its potential as an alternative therapy, particularly for those who cannot access enzyme replacement therapy.
In a groundbreaking case series of 29 patients, investigators discovered significant biochemical changes associated with the repurposing of ambroxol in patients with Gaucher disease. The study, which followed patients over a mean duration of 2.6 years, revealed remarkable improvements in hematologic parameters, visceral volumes, and plasma biomarkers.1
Gaucher disease is a rare genetic disorder characterized by the accumulation of glucocerebroside in various organs, leading to a range of debilitating symptoms. Enzyme replacement therapy is the current standard treatment for the disease, but its high cost poses a significant barrier to many patients, particularly in resource-limited settings.
Investigators led by Xia Zhan, MM, of the Department of Pediatric Endocrinology and Genetics, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, sought to evaluate the efficacy and safety of ambroxol, a drug traditionally used as a mucolytic agent, in patients the rare disease who had not received any disease-specific treatment.
Ambroxol had previously been identified as a potential enhancer of stability and residual activity of misfolded glucocerebrosidase variants in a 2009 study.
Of the 32 enrolled patients, 28 completed the study, with 26 demonstrating positive responses to ambroxol treatment. The results showed notable improvements in multiple aspects of the disease. Hemoglobin concentration increased significantly from a mean of 10.4 - 11.9 g/dL, and platelet count improved from 69 - 78 × 10^3/µL. The mean spleen volume decreased from 17.47 - 12.31 multiples of normal (MN), while the mean liver volume decreased from 1.90 - 1.50 MN.
The study also observed favorable changes in key plasma biomarkers with promising findings. Chitotriosidase activity decreased by 43.1%, and glucosylsphingosine levels decreased by 34.1%. Investigators noted these biomarker changes validate the positive impact of ambroxol on Gaucher disease.
Improvements were more pronounced among patients with milder symptoms and those who initiated ambroxol treatment at a younger age. Patients who started treatment at an average age of 6.3 years experienced more rapid improvements in hemoglobin concentration, platelet count, chitotriosidase activity, and glucosylsphingosine levels.
However, limitations and challenges in treatment response were noted in an editorial commentary. The need for new therapies and further research, as well as collaborative efforts in order to enhance understanding and provide affordable care for GD patients worldwide, was acknowledged.2
The study highlights the safety of long-term ambroxol treatment, with only three patients experiencing mild and transient adverse events. This finding further supports the potential of ambroxol as an alternative therapy for Gaucher disease, particularly in cases where enzyme replacement therapy is not feasible.1
The results of this case series provided compelling evidence for the repurposing of ambroxol as a therapeutic option for Gaucher disease patients. The study stated that further research is needed to validate these findings in larger and more diverse patient populations, but it offers hope for individuals with Gaucher disease who face limited treatment options due to financial constraints.
"Our findings indicate that long-term treatment with ambroxol can lead to significant improvements in hematologic parameters, visceral volumes, and plasma biomarkers among patients with Gaucher disease,” investigators wrote. “These results have the potential to transform the management of this rare genetic disorder, especially for those who cannot access enzyme replacement therapy."