Researchers at Lawson Research Institute have demonstrated that Ambroxol, a cough medicine widely used in Europe, may slow the progression of dementia in people with Parkinson's disease. The 12-month randomized clinical trial, published in JAMA Neurology, represents a significant step toward addressing a condition that affects approximately half of Parkinson's patients within 10 years of diagnosis.
The study, led by Dr. Stephen Pasternak, a cognitive neurologist at Parkwood Institute and St Joseph's Health Care London, enrolled 55 participants with Parkinson's disease dementia. "Our goal was to change the course of Parkinson's dementia," Pasternak said. "This early trial offers hope and provides a strong foundation for larger studies."
Clinical Trial Results Show Protective Effects
The trial divided participants into two groups, with one receiving daily Ambroxol and the other a placebo. Researchers monitored memory, psychiatric symptoms, and GFAP, a blood marker linked to brain damage throughout the 12-month period.
Key findings revealed that Ambroxol was safe, well-tolerated, and reached therapeutic levels in the brain. Most notably, psychiatric symptoms worsened in the placebo group but remained stable in those taking Ambroxol. Participants carrying high-risk GBA1 gene variants showed improved cognitive performance when treated with Ambroxol.
The study also found that GFAP levels increased in the placebo group but stayed stable with Ambroxol treatment, suggesting potential brain protection. This biomarker finding provides objective evidence of the drug's neuroprotective effects.
Targeting the Underlying Disease Mechanism
Ambroxol works by supporting glucocerebrosidase (GCase), a key enzyme produced by the GBA1 gene. In people with Parkinson's disease, GCase levels are often low, and when this enzyme doesn't function properly, waste accumulates in brain cells, leading to damage.
"Current therapies for Parkinson's disease and dementia address symptoms but do not stop the underlying disease," Pasternak explained. "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."
Pasternak's interest in Ambroxol originated during a fellowship at The Hospital for Sick Children in Toronto, where the drug was identified as a treatment for Gaucher disease, a rare genetic disorder in children caused by GCase deficiency.
Addressing an Urgent Medical Need
Parkinson's disease dementia causes memory loss, confusion, hallucinations, and mood changes, profoundly affecting patients, families, and the healthcare system. About half of those diagnosed with Parkinson's develop dementia within 10 years, creating an urgent need for effective treatments.
Although Ambroxol is approved in Europe for treating respiratory conditions and has a long-standing safety record, including use at high doses and during pregnancy, it is not approved for any use in the United States or Canada.
Future Research Directions
The Weston Foundation funded this study, which represents an important step toward developing new treatments for Parkinson's disease and other cognitive disorders, including dementia with Lewy bodies. Pasternak and his team plan to initiate a follow-up clinical trial focused specifically on cognition later this year.
"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."
