Ambroxol — a chest congestion and cough medicine that’s being investigated for the treatment of Gaucher disease — has several molecular mechanisms in addition to acting as an enhancer of the enzyme that’s lacking in Gaucher patients.
These mechanisms might also act to alter the disease course in patients with Parkinson’s disease, a neurodegenerative condition affecting many Gaucher patients, researchers from University College London in the U.K. argued in their study, published in the journal Scientific Reports.
Earlier research had indicated that the expectorant ambroxol is beneficial for Gaucher disease patients, as it acts to boost the activity of the faulty glucocerebrosidase enzyme. When mutated, the enzyme fails to break down the fatty substance glucocerebroside, which accumulates in so-called lysosomes in the body.
These mutations are also associated with Parkinson’s disease.
In an effort to examine if ambroxol may impact brain processes linked to these Gaucher mutations, researchers studied lab-grown neurons from mice. They noted that ambroxol treatment boosted enzyme function, as had been observed in earlier studies. This impacted the content of lysosomes, as would be expected.
But the team’s experiments showed that the medication has actions more complex than that. It blocked a process called autophagy, which cells use to degrade and recycle old or unwanted cell components.
The treatment also impacted mitochondria — the cellular power plants that convert nutrients into energy. Other studies show that natural supplements, which improve mitochondrial function, improve Gaucher processes. Mitochondria are also believed to be abnormal in Parkinson’s disease.
It also triggered a greater release of the Parkinson’s disease-associated protein alpha-synuclein. In Parkinson’s, this protein aggregates inside cells.
Since researchers know that the protein is transferred out of cells with the help of a process called exocytosis, researchers also examined whether ambroxol impacted the transportation mechanism. Just as they had suspected, they noted that ambroxol boosted the process.
They also looked at whether these effects were dependent on the activity of the glucocerebrosidase enzyme, and found that some, including the altered lysosomal function and altered mitochondrial function, were not, suggesting the treatment should be studied further as a potential treatment.