A cough medicine used for decades in Europe called ambroxol has shown promise for treating dementia in people with Parkinson's disease. The corresponding study was published in JAMA Neurology.
People with Parkinson's disease often have low levels of a key enzyme called glucocerebrosidase (GCase), which is produced by the GBA1 gene. When this enzyme is deficient, waste accumulates inside brain cells, resulting in damage. Ambroxol is a chaperone for GCase and increases levels of the enzyme. The researchers behind the current study thus sought to see whether the drug could benefit Parkinson's-related conditions.
To do so, they conducted a phase 2, placebo-controlled, randomized clinical trial including 55 patients with Parkinson's disease who had the condition for at least one year before cognitive impairment. Participants also had mild to moderate dementia, were taking stable medications, and were aged 50 years and older. Altogether, 31 individuals received ambroxol and 24 received a placebo. The trial ran for 52 weeks.
Ultimately, the researchers found that ambroxol was safe and well-tolerated, and that it reached therapeutic levels in the brain. Whereas the marker of brain cell damage (GFAP) increased in the placebo group, levels remained stable among those taking ambroxol. Similar observations were made for psychiatric symptoms; they worsened in the placebo group yet remained stable among those taking ambroxol. The researchers further found that cognitive performance improved among participants with high-risk GBA1 gene variants.
"Current therapies for Parkinson's disease and dementia address symptoms but do not stop the underlying disease. These findings suggest ambroxol may protect brain function, especially in those genetically at risk. It offers a promising new treatment avenue where few currently exist," lead author of the study, Dr. Stephen Pasternak, Director of the Cognitive Neurology and Alzheimer’s Disease Research Centre at the Parkwood Institute in Ontario, Canada, said in a press release.
While ambroxol has been approved in Europe for respiratory conditions, it has not been approved in the US or Canada for any use.
Pastarnak and his team now intend to commence a follow-up clinical trial focusing on cognition later this year.
Sources: EurekAlert, JAMA Neurology