Cough syrup as a potential treatment for Parkinson’s disease-related dementia

A randomized clinical trial published in JAMA Neurology suggests that a cough syrup sold in Europe is safe and well tolerated in patients with Parkinson’s disease and may provide improvements in cognitive performance.The cough syrup, Ambroxol, is an expectorant available over-the-counter in Europe but not approved in Canada, the U.K. or the U.S. It increases levels of a lysosomal enzyme, beta-glucocerebrosidase (GCase), which is often low in people with Parkinson’s disease. GCase cleaves the glycolipid beta-glucocerebroside, and animal studies suggest when it is not active, waste builds up in brain cells, leading to damage. The idea of the trial was to explore if increasing GCase could improve Parkinson’s disease dementia symptoms.“Our goal was to change the course of Parkinson’s dementia,” said Dr. Stephen Pasternak, a scientist at Lawson Research Institute professor of neurology at Schulich School of Medicine and Dentistry at Western University in London, Ont. “This early trial offers hope and provides a strong foundation for larger studies.”Fifty-five patients with mild to moderate Parkinson’s disease-related dementia were randomized to Ambroxol once daily or placebo and followed for 52 weeks. The treatment was found to be safe and well-tolerated, with mild to moderate gastrointestinal upset as the main adverse event attributed to Ambroxol.While there was no significant effect of Ambrosol on Alzheimer’s Disease Assessment Scale–cognitive subscale (ADAS-Cog) after 52 weeks, neuropsychiatric Inventory (NPI) scores increased in the group taking the placebo, but not in the Ambroxol group. The GBA1 gene encodes GCase. Patients with Parkinson’s disease who have a GBAI gene variant tend to experience earlier onset and an increased risk of cognitive decline. In the study, those with the GBAI gene variant taking Ambroxol showed an improvement in cognitive performance scores (i.e., ADAS-Cog) compared people with the GBAI gene variants taking placebo. Also, a marker of brain cell damage, plasma glial fibrillary acidic protein (GFAP), increased in the placebo group but stayed stable in the Ambroxol group, suggesting Ambroxol may protect brain function.“Current therapies for Parkinson’s disease and dementia address symptoms but do not stop the underlying disease,” explained Pasternak. “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.”The authors of the study note that there are three other clinical trials currently examining the effects of Ambroxol in people with Parkinson’s disease:Ambroxol to Slow Progression in Parkinson Disease [ASPro-PD]Ambroxol in New and Early Dementia with Lewy Bodies, A Phase IIa Multicentre Randomized Controlled Double Blind Clinical Trial [ANeED]AMBITIOUS, a randomized phase II clinical trial in carriers of the GBA1 gene variantResearchers at the Hospital for Sick Children previously studied Ambroxol as a treatment for Gaucher disease, a genetic disorder caused by a deficiency in GCase.

Cough syrup as a potential treatment for Parkinson’s disease-related dementia

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