Treating Dementia with Cough Medicine: A Double Blind Randomized Controlled Trial Repurposing Ambroxol as a Disease Modifying Treatment for Parkinson’s Disease Dementia

2014  -  London, ON, CA


The University of Western Ontario, Lawson Research Health Institute, Parkwood Hospital London, London Health Sciences Centre

Project description

Currently there are no effective treatments for cognitive impairment in Parkinson’s Disease Dementia (PDD). Furthermore, existing treatments do not address the underlying cause of the PDD including the accumulation of pathological protein aggregates in the brain.  This trial will assess the drug Ambroxol as a disease-modifying therapy for PDD. Ambroxol is a cough medicine with an excellent safety record that is available over the counter throughout the world. Ambroxol has been found to increase the levels of an enzyme called β-Glucocerebrosidase (GCase). Increasing the levels of GCase in animal and cell cultures reduces the buildup of pathological proteins, suggesting that this strategy may improve the outcome in PDD.

We will randomize 75 patients to receive Ambroxol at either 525 mg/day or 1050 mg/day, or placebo for 1 year. Patients will be followed with tests commonly used to assess memory and motor function.  We will also look for evidence that Ambroxol is changing the course of the disease by examining proteins in cerebrospinal fluid and changes in brain size and chemistry. The levels of Ambroxol and GCase in blood and cerebrospinal fluid will be measured confirm that the medication is getting into the brain and that it is having an effect. We hope that this medication will improve patient function or slow down the course of PDD.

Relevance to the acceleration of therapeutics for neurodegenerative diseases of aging

Treatments that effect long term course of dementia represent a critical unmet need.  Dementia with alpha-synuclein protein aggregation include Parkinson’s disease, Parkinson’s disease dementia, and Lewy Body Dementia.  These diseases affect more that 1/3 of patients in memory clinics.  Up to half of Parksinon’s disese patients will also develop cognitive impairment.

Developing a new drug often requires decades of safety testing and development. By repurposing a Ambroxol, a drug with proven safety and that is already available, we will leap frog over the many years of preclinical work to bring this drug into clinical trials, and hopefully to patient care.

Anticipated outcome

To date, treatments for Parkinson’s disease and dementia have only been effective at improving the symptoms of these diseases.  In this study, we are targeting a novel protein called Glucocerebrosidase (GCase), which we believe will reduced pathological protein aggregates.  By using Ambroxol to increase the levels of this enzyme, we hope that we will and prevent the progression and may even improve symptoms in Parksinon’s disease dementia. If effective, this will be the first disease modifying therapy for dementia.