An initial study from Japan demonstrated that oral ambroxol may help treat forms of Gaucher disease characterized by neurological symptoms. The study, “Ambroxol chaperone therapy for neuronopathic Gaucher disease: A pilot study,“ was published in the journal, Annals of Clinical and Translational Neurology.
Ambroxol is used to treat respiratory diseases that cause excessive mucus. It is found in several approved medications, including Mucosolvan, Mucobrox, Mucol, Lasolvan, Mucoangin, Surbronc, Ambolar, and Lysopain. It breaks down mucopolysaccharide fibers.
In Gaucher’s disease, glucocerebroside, a type of fatty substance, accumulates in cells and does not get broken down by lysosomes (a lysosome is a part of a cell that breaks down molecules). People with Gaucher’s disease consequently have fatigue, bruising, anemia, enlarged organs, and other symptoms.
Although therapies exist that help remove glucocerebroside, they have little effect on neurological symptoms of Gaucher’s disease. Ambroxol could aid in the breakdown of glucocerebroside and may help with neurological symptoms because it crosses the blood-brain barrier, a system of cells that prevent certain molecules from entering the central nervous system. The blood-brain barrier provides protection from toxins and harmful substances, but can also prevent certain drugs from affecting the nervous system.
Scientists, led by Aya Narita of the Division of Child Neurology, Institute of Neurological Science, Tottori University Faculty of Medicine in Yonago, Japan, studied five people with Gaucher disease in a pilot, proof-of-concept study. The participants received a high dose of oral ambroxol along with enzyme-replacement therapy, a standard treatment.
The medication was safe and well-tolerated overall, meeting the study’s primary purpose. It was seen to increase the activity of an enzyme that breaks down glucocerebroside, known as glucocerebrosidase. Importantly, ambroxol crossed the blood-brain barrier and decreased glucosylsphingosine in the cerebrospinal fluid, a measure of Gaucher disease activity. Disease symptoms also decreased, specifically muscle jerkiness, seizures, and problems with the pupil light reflex. Two patients regained the ability to walk, due to decreases in muscle spasms and contractions caused by the disorder (myoclonus).
“Pharmacological chaperone therapy with high-dose oral ambroxol shows promise in treating neuronopathic [Gaucher disease], necessitating further clinical trials,” the researchers concluded.
This initial study shows promise. Further large-scale studies in humans will be needed, however, to confirm the potential of ambroxol for treating neurological aspects of Gaucher disease.