The results of a phase 2 clinical trial of ambroxol in Canada for people with Parkinson’s dementia were published recently, finding it was safe and tolerable when taken by participants.
A proportion of people with Parkinson’s experience cognitive changes – changes to our memory, thinking, and behaviours – as the condition progresses. The severity of these changes differs from person to person; however, when they are significant enough to impair daily life, an individual may be diagnosed with Parkinson’s dementia. It is estimated that 20-40% of people with Parkinson’s may develop an associated dementia, and this risk increases the longer someone is living with Parkinson’s (1).
Despite this prevalence, the treatments for Parkinson’s dementia, especially those that can slow or prevent cognitive changes, are currently lacking. To help address this, researchers at Western University in Canada conducted a phase 2 clinical trial of ambroxol – a cough medicine – in people with Parkinson’s dementia to determine whether the drug was safe and tolerable when taken by participants. They also examined if it could improve or slow the progression of cognitive symptoms. 55 people participated in this 52-week study and were randomly assigned to receive either a high or low dose of ambroxol or a placebo (dummy drug).
What is ambroxol?
Ambroxol is currently licensed in some European countries as a cough medicine; however, researchers believe it may also have a disease-modifying effect in people with Parkinson’s. This is because ambroxol directly affects the activity of the enzyme glucocerebrosidase, or ‘GCase’, which helps the cell break down and dispose of waste. There is evidence of a relationship between lower GCase activity and a higher risk of developing Parkinson’s; furthermore, variations to the GBA1 gene – the gene that provides the instructions for building GCase – are the most common genetic risk factor for Parkinson’s. These variations can cause lower GCase production. Thus, researchers are interested in whether drugs like ambroxol, which increase GCase activity, could help rescue neurons and consequently slow Parkinson’s progression.
What are the results?
Overall, the researchers found that ambroxol was safe and tolerable when taken by participants. They saw a worsening of cognitive symptoms in those taking the placebo while symptoms appeared to stabilise in those taking ambroxol. This difference, however, was not clinically meaningful. Further research will be needed to confirm whether ambroxol can slow or stop progression of cognitive symptoms in people with Parkinson’s dementia.
Some of the trial participants were carriers of a GBA1 genetic variant. GBA1 is the gene which provides the instructions for building the enzyme GCase; GCase is the enzyme that ambroxol directly acts on and increases the activity of. In the study, individuals with GBA1 variants performed better on a few of the cognitive tests. However, the number of people with this variant in the trial was too small to draw any solid conclusions. Therefore, the researchers suggest that future trials of ambroxol should involve more GBA1 carriers to better assess whether it has a stronger effect in that population.
Why is this study important?
Although the team did not see a significant change in cognitive symptoms, the results provided interesting indications that warrant further investigation, especially in those with GBA1 variations. In the ongoing phase 3 trial of ambroxol, ASPro-PD, half of the 330-participant cohort will involve people with GBA1 variations. This will hopefully provide further clarity on this. In addition, cognitive tests will be part of the overall assessment process in the ASPro-PD study, giving researchers more insight on whether ambroxol can slow cognitive changes in people with Parkinson’s.
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