In a small clinical trial in Canada, a medicine commonly found in European cough syrups has shown early signs it might do something no approved treatment for Parkinson’s disease dementia has yet achieved: help slow the disease’s progression in the brain.
The drug is Ambroxol. It’s been used for decades to treat respiratory ailments by thinning mucus and easing coughs. But now, researchers at St. Joseph’s Health Care London and its Lawson Research Institute believe this everyday remedy might be able to do much more. At least for certain patients.
“Our goal was to change the course of Parkinson’s dementia,” said Dr. Stephen Pasternak, the cognitive neurologist who led the trial. “This early trial offers hope and provides a strong foundation for larger studies.”
From Cough Relief to a Neurological Aid
Parkinson’s disease dementia is a debilitating condition that emerges in up to half of all Parkinson’s patients within ten years of diagnosis. It brings memory loss, hallucinations, and mood changes. Once it sets in, the decline can be relentless, and until now, no treatment has reliably slowed its march.
But the 12-month clinical trial published in JAMA Neurology hints that Ambroxol may help delay that progression, especially in people with specific genetic vulnerabilities.
In the double-blind trial, 55 people with Parkinson’s disease dementia were given either Ambroxol or a placebo. Researchers tracked their cognitive function, psychiatric symptoms, and levels of a brain damage marker in the blood known as GFAP.
While Ambroxol didn’t significantly improve memory test scores in the full group compared to placebo, it did stabilize GFAP levels, suggesting it may help protect the brain from ongoing damage. Psychiatric symptoms worsened in the placebo group but held steady in those who received the drug.
Intriguingly, the subgroup of patients carrying mutations in a gene called GBA1, which is known to raise Parkinson’s risk, responded more clearly. These individuals not only showed stable psychiatric profiles but also demonstrated notable improvements in cognitive test scores.
“These findings suggest Ambroxol may protect brain function, especially in those genetically at risk,” said Pasternak. “It offers a promising new treatment avenue where few currently exist.”
The Enzyme Link and Why It Matters
Ambroxol’s appeal lies in its ability to help cells produce more of a crucial enzyme called glucocerebrosidase (GCase). This enzyme, encoded by the GBA1 gene, helps cells break down waste. When GCase is in short supply (as it often is in people with Parkinson’s), the buildup of cellular debris can damage brain cells and accelerate neurodegeneration.
Ambroxol seems to act as a molecular chaperone, helping GCase fold correctly and reach the parts of the cell where it’s needed. In this trial, participants on high-dose Ambroxol showed higher GCase levels than those on placebo.
Though the primary results showed no significant difference in cognitive performance between the groups overall, the trial wasn’t large enough to draw conclusions about GBA1 carriers, who made up just eight of the participants. But in this smaller group, the effects were hard to ignore. Three out of five carriers on Ambroxol saw large improvements — up to 11 points — on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), a standard test of memory and cognition.
“Although this sample is too small to support any conclusion,” the study authors wrote, “these findings are highlighted given the proposed action mechanism of Ambroxol in GCase activity that is particularly lower in carriers of the GBA1 gene variant.”
Not a Cure, but a Clue
Still, caution is warranted. In the full cohort, Ambroxol did not outperform placebo on primary cognitive endpoints at 26 or 52 weeks. That doesn’t mean it isn’t working. It may just mean researchers need more time or more precisely selected participants to see its effects.
“Primary outcome measures did not support therapeutic effects of Ambroxol on cognition in Parkinson’s disease dementia,” the authors noted, “although there may have been stabilization of neuropsychiatric symptoms.”
Importantly, both the drug and the disease are complex. Parkinson’s dementia unfolds differently depending on a person’s genetic makeup and the underlying biological mechanisms. That’s why future trials, Pasternak said, should focus on recruiting more GBA1 carriers, where Ambroxol’s mechanism might have the best shot at showing its potential.
Meanwhile, Pasternak and his team are already planning a follow-up study focused specifically on cognitive changes and tailored to this genetic subgroup.
“This research is vital because Parkinson’s dementia profoundly affects patients and families,” Pasternak said. “If a drug like Ambroxol can help, it could offer real hope and improve lives.”
Why Haven’t You Heard of This Drug?
Ambroxol is not approved for human use in the United States or Canada. In Europe, it’s widely sold over the counter as a cold medicine. In some parts of the world, it’s even used in veterinary medicine for horses and dogs.
Its reputation as a safe drug, with a long-standing track record and tolerability even at high doses, makes it an attractive candidate for repurposing. But regulatory hurdles remain. In North America, Ambroxol is currently available only for research purposes, though its use in Europe spans decades.
Researchers in Australia are also testing Ambroxol in people with motor neurone disease, including ALS. And at least three major clinical trials are underway globally: ASPro-PD, ANeED, and AMBITIOUS, each exploring Ambroxol’s effects on different neurodegenerative diseases and patient populations.
Neurodegenerative diseases are notoriously difficult to treat, let alone cure. Most existing therapies manage symptoms without altering the disease’s trajectory. The idea that a decades-old cough syrup could do more (particularly for a genetic subset of patients) is as surprising as it is hopeful.
And it raises a broader point about the future of dementia care: precision medicine may not always come in the form of new drugs. Sometimes, it might begin with reexamining the ones we already have.
The next step for Ambroxol is a larger, better-targeted trial.
