A recent clinical trial has unveiled promising results for Ambroxol, a widely used cough medicine in Europe, suggesting it may slow cognitive decline in individuals with Parkinson’s disease dementia. Conducted over 12 months, the study found that Ambroxol not only stabilized psychiatric symptoms but also protected against brain damage and improved cognition in participants genetically predisposed to the disease.
Ambroxol enhances the activity of an enzyme known as GCase, which is typically deficient in Parkinson’s patients, leading to brain cell damage. Although not yet approved for use in North America, the drug’s established safety profile and initial benefits position it as a compelling candidate for further research.
Clinical Trial Insights
The trial, published in JAMA Neurology, was led by Dr. Stephen Pasternak at the Lawson Research Institute, the research arm of St. Joseph’s Health Care London. It involved 55 participants with Parkinson’s disease dementia, a condition characterized by memory loss, confusion, hallucinations, and mood changes. Approximately half of those diagnosed with Parkinson’s develop dementia within a decade, posing significant challenges for patients, families, and healthcare systems.
Participants were divided into two groups, with one receiving daily doses of Ambroxol and the other a placebo. The study aimed to alter the progression of Parkinson’s dementia, a goal that Dr. Pasternak describes as offering hope and laying a strong foundation for larger studies.
Key Findings
- Safety and Tolerance: Ambroxol was found to be safe, well-tolerated, and reached therapeutic levels in the brain.
- Psychiatric Stability: While psychiatric symptoms worsened in the placebo group, they remained stable in those taking Ambroxol.
- Genetic Advantage: Participants with high-risk GBA1 gene variants showed improved cognitive performance on Ambroxol.
- Brain Protection: A marker of brain cell damage, GFAP, increased in the placebo group but remained stable in those taking Ambroxol, indicating potential brain protection.
Understanding the Mechanism
Ambroxol supports the enzyme glucocerebrosidase (GCase), produced by the GBA1 gene. In Parkinson’s patients, GCase levels are often low, leading to the accumulation of waste in brain cells and subsequent damage. Dr. Pasternak’s interest in Ambroxol was piqued during his 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 a GCase deficiency.
Applying this knowledge, Dr. Pasternak is exploring whether boosting GCase with Ambroxol could protect the brain in Parkinson’s-related diseases. According to him, “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.”
Implications and Future Research
The study, funded by the Weston Foundation, marks a significant step towards developing new treatments for Parkinson’s disease and other cognitive disorders, including dementia with Lewy bodies. Dr. Pasternak and his team plan to initiate a follow-up clinical trial later this year, focusing specifically on cognition.
Despite its approval in Europe for respiratory conditions and its long-standing safety record, including use at high doses and during pregnancy, Ambroxol is not yet approved for any use in Canada or the U.S. The potential for Ambroxol to offer a safe, affordable treatment for slowing dementia progression is especially significant given the current lack of such options.
As Dr. Pasternak emphasizes, “This research is vital because Parkinson’s dementia profoundly affects patients and families. If a drug like Ambroxol can help, it could offer real hope and improve lives.”
As the scientific community eagerly awaits the results of future trials, the initial findings from this study provide a glimmer of hope for those affected by Parkinson’s disease dementia and their families, potentially paving the way for new, effective treatments in the near future.
