Cough Medicine Shows Promise Against Parkinson’s Dementia

A common European cough medicine has shown encouraging signs of slowing brain damage in people with Parkinson’s disease dementia, according to a clinical trial published in JAMA Neurology.

The 12-month study of 55 participants found that Ambroxol—used safely for decades to treat respiratory conditions—helped stabilize psychiatric symptoms and may protect brain cells from the progressive damage that characterizes this devastating condition.

The research addresses a critical unmet need, as roughly half of people diagnosed with Parkinson’s disease develop dementia within 10 years, causing memory loss, confusion, hallucinations, and mood changes that profoundly impact patients and families.

“Our goal was to change the course of Parkinson’s dementia,” explains Dr. Stephen Pasternak, the cognitive neurologist at Lawson Research Institute who led the study. “This early trial offers hope and provides a strong foundation for larger studies.”

Targeting Brain Cleanup Systems

The trial investigated whether boosting a key cellular cleanup enzyme could protect against brain degeneration. Ambroxol works by supporting glucocerebrosidase (GCase), an enzyme that helps brain cells dispose of waste products. When GCase doesn’t function properly, toxic materials accumulate and damage neurons.

People with variations in the GBA1 gene—which produces GCase—face heightened risk for Parkinson’s dementia. The research team hypothesized that chemically enhancing this enzyme could slow disease progression, similar to how Ambroxol treats rare genetic disorders in children.

A crucial detail not emphasized in the press release: The study demonstrated clear “target engagement,” with β-glucocerebrosidase levels significantly higher in the Ambroxol group (12.45 nmol/h/mg) compared to placebo (8.50 nmol/h/mg) at 26 weeks, confirming the drug reached therapeutic levels and affected its intended target.

Promising but Mixed Results

While Ambroxol didn’t show dramatic cognitive improvements across all participants, the results revealed several encouraging patterns:

• Psychiatric symptoms worsened in the placebo group but remained stable with Ambroxol treatment
• Participants with high-risk GBA1 gene variants showed improved cognitive performance on Ambroxol
• Brain damage markers (GFAP) increased in placebo patients but stayed stable with treatment
• The drug proved safe and well-tolerated, with only mild gastrointestinal side effects

A Different Approach

The study represents a shift from symptom management toward disease modification. Current Parkinson’s treatments primarily address movement problems and cognitive symptoms without targeting underlying brain degeneration.

“Current therapies for Parkinson’s disease and dementia address symptoms but do not stop the underlying disease,” Pasternak notes. “These findings suggest Ambroxol may protect brain function, especially in those genetically at risk.”

The medication’s established safety profile offers a significant advantage. Ambroxol has been used safely for decades in Europe, including at high doses and during pregnancy, though it remains unapproved in Canada and the United States.

Building on Rare Disease Research

Pasternak’s interest in Ambroxol stems from pediatric research at Toronto’s Hospital for Sick Children, where the drug showed promise treating Gaucher disease—a rare genetic condition caused by GCase deficiency. This connection between rare and common diseases illustrates how research across different patient populations can yield unexpected therapeutic insights.

The enzyme dysfunction that causes devastating symptoms in children with Gaucher disease appears to contribute more subtly to Parkinson’s dementia, suggesting that treatments effective for rare genetic disorders might benefit much larger patient populations.

Next Steps

The research team, funded by the Weston Foundation, plans to launch a follow-up trial focused specifically on cognitive outcomes later this year. The current study provides crucial safety data and dosing information needed for larger, definitive trials.

For families facing Parkinson’s dementia, the results offer measured hope. While not a cure, the possibility of slowing brain damage with a well-tolerated medication represents meaningful progress in a field where effective treatments remain desperately needed.