August 1, 2025
Scientists have been studying a kind of cough medicine called ambroxol to determine if it might be a promising treatment for Parkinson’s disease dementia (PDD), one of the two major forms of Lewy body dementia (LBD). This might seem unusual at first, but the reason researchers are interested in this drug is based on a clue from genetics. People with certain variants of the GBA1 gene are known to be at increased risk for PDD. This gene codes for a protein called GCase, and ambroxol interacts with GCase in a way that researchers believe may be beneficial in slowing disease progression.
A group of Canadian researchers has now reported the results of a small clinical trial of ambroxol in people with mild to moderate PDD.
How was the study designed?
The study enrolled a total of 55 people. These volunteers were randomly assigned to receive either a low or high dose of ambroxol or a placebo for 1 year. During the trial, volunteers completed 11 clinic visits, and researchers checked for safety as well as measuring cognition, movement, neuropsychiatric features, and fluctuations. The volunteers also gave samples of blood and cerebrospinal fluid so that scientists could perform laboratory tests.
What did the study show?
The good news is that the study showed that the drug was safe. Overall, the study suggests that the main side effect was mild to moderate stomach upset.
However, the results did not provide clear evidence of benefit. In comparing the groups of volunteers who took ambroxol and those who took placebo, the differences were small enough that it cannot be ruled out that they occurred by random chance rather than reflecting a true effect of the drug. This is common in small studies such as this one and does not necessarily mean that the drug is ineffective, just that we can’t know for sure until larger studies are completed.
Given the relationship of ambroxol to the GCase protein, the scientists paid special attention to a small handful of volunteers in the study who turned out to have risk variants in their GBA1 genes. Intriguingly, three of them showed improvements in cognition and three of them showed improvements in neuropsychiatric symptoms. Unfortunately, the sample size for these variant carriers was too small to say for certain that this is a real effect.
The researchers also found an intriguing result in a laboratory blood test for the protein GFAP, which is a marker of neurodegeneration, that is, loss of brain cells. Among volunteers in the placebo group GFAP levels increased during year-long trial, but they remained stable in volunteers taking ambroxol. Moreover, this group difference was large enough that the researchers are confident that it represents a true drug effect and may indicate that ambroxol could be protective against neurodegeneration.
What’s next?
This small trial suggests that ambroxol is safe for people with PDD but did not provide clear evidence of benefit. However, results from the volunteers with risk variants in GBA1 are intriguing, particularly given that ambroxol interacts with the protein encoded by GBA1. The effect of the drug on the marker of neurodegeneration, GFAP, is also promising. A reasonable next step would be to perform another trial, either with a larger sample size or perhaps focused on people with GBA1 gene variants.
In addition, ambroxol is still being studied in clinical trials for Parkinson’s disease and LBD in the UK, Norway, and Australia, and the results from those studies may shed further light.
How can I get involved?
Finding safe and effective treatments for Lewy body dementia takes research, and research takes people like you.
For more information on clinical trials and other studies that might be right for you, LBDA encourages you to visit our clinical trials page. To stay up-to-date on new studies when they launch, you can also sign up for LBDA’s Lewy Trial Tracker.
REFERENCE
Carolina R. A. Silveira CRA, Coleman KKL, Borron K, et al. 2025. Ambroxol as a treatment for Parkinson disease dementia: A randomized clinical trial. JAMA Neurology, online ahead of print. DOI: 10.1001/jamaneurol.2025.1687.