While Ambroxol, a medication primarily recognized in Europe for its efficacy in managing respiratory ailments and boasting a well-established safety profile that includes high-dose administration and use during gestation, has not received regulatory approval for any therapeutic application within the United States or Canada.
Ball-and-stick model of ambroxol molecule. Image credit: Marina Vladivostok / ChemSpider.
The cognitive decline associated with Parkinson’s disease dementia manifests as impaired recall, disorientation, perceptual disturbances, and emotional lability.
Approximately fifty percent of individuals diagnosed with Parkinson’s disease experience the onset of dementia within a decade, imposing a significant burden on patients, their kin, and the healthcare infrastructure.
“Our overarching objective was to alter the trajectory of cognitive impairment in Parkinson’s disease,” stated Dr. Stephen Pasternak, a specialist in cognitive neurology affiliated with Parkwood Institute, St Joseph’s Health Care London, and Robarts Research Institute.
“This preliminary investigation offers a glimmer of hope and establishes a robust groundwork for subsequent, larger-scale investigations.”
The clinical trial, spanning a period of twelve months, enrolled fifty-five participants afflicted with Parkinson’s disease dementia.
A portion of these participants were administered daily doses of Ambroxol, whereas the control group was provided with a placebo.
Assessments encompassed the monitoring of memory function, psychiatric manifestations, and GFAP, a biomarker in the bloodstream indicative of neuronal injury.
The research team reported that Ambroxol demonstrated a favorable safety profile, was well-tolerated by participants, and successfully attained therapeutically relevant concentrations within the central nervous system.
A deterioration in psychiatric symptoms was observed in the placebo group, contrasted by stability in individuals receiving Ambroxol.
Cognitive performance showed enhancement among participants carrying high-risk variants of the GBA1 gene when treated with Ambroxol.
An elevation in GFAP levels was noted in the placebo cohort, while levels remained consistent in the Ambroxol group, suggesting a potential protective effect on brain tissue.
“Existing therapeutic interventions for Parkinson’s disease and its associated dementia primarily aim to alleviate symptoms, rather than arresting the progression of the underlying pathology,” Dr. Pasternak commented.
“These findings indicate that Ambroxol may serve to safeguard cerebral function, particularly in individuals with a genetic predisposition. It presents a promising new therapeutic avenue in a domain where options are currently scarce.”
Ambroxol plays a supportive role for glucocerebrosidase (GCase), a crucial enzyme encoded by the GBA1 gene.
In individuals with Parkinson’s disease, GCase activity often diminishes. Inadequate functioning of this enzyme results in the accumulation of cellular debris within neurons, precipitating neuronal damage.
“This research holds considerable importance due to the profound impact of Parkinson’s dementia on the lives of patients and their families,” emphasized Dr. Pasternak.
“Should a compound like Ambroxol prove beneficial, it could provide tangible hope and considerably improve the quality of life for affected individuals.”
The findings have been published in the esteemed journal JAMA Neurology.
_____
Carolina R. A. Silveira et al. Ambroxol as a Treatment for Parkinson Disease Dementia: A Randomized Clinical Trial. JAMA Neurol, published online June 30, 2025; doi: 10.1001/jamaneurol.2025.1687
