A common ingredient in cough syrup, ambroxol, is being tested as a treatment for Parkinson’s disease. Researchers led by a team at UCL will soon launch a Phase 3 clinical trial to assess the effectiveness of the drug in 330 people with the disease.
“I am delighted to be leading this exciting project,” said study lead Professor Anthony Schapira in a statement. “This will be the first time a drug specifically applied to a genetic cause of Parkinson’s disease has reached this level of trial and represents ten years of extensive and detailed work in the laboratory and in a proof of principle clinical trial.”
Ambroxol is a type of cough medicine known as an expectorant. It works by thinning down the sticky phlegm build-up caused by respiratory diseases such as bronchitis, making it easier for patients to clear their congestion by coughing. But a 2009 study planted the seed that could lead to a whole other use for this drug.
The study found that ambroxol increased the levels of an enzyme called glucocerebrosidase (GCase) in patients with a rare genetic disorder, Gaucher disease. People with this condition are also at higher risk of developing Parkinson’s disease, although scientists still don’t completely understand the connection.
A typical feature of Parkinson’s disease is the accumulation of Lewy bodies – clusters of a protein called α-synuclein – in certain regions of the brain. When α-synuclein levels go up, GCase levels go down. So, when the 2009 paper showed that ambroxol was able to increase GCase levels in patients with Gaucher disease, researchers began to wonder if it might have the same effect in Parkinson’s disease, and – crucially – whether that might indirectly lower the levels of problematic α-synuclein.
A small human trial has already been performed by Professor Schapira’s team, and the results were encouraging. Ambroxol was able to get into the brain (no easy feat!), increasing the levels of GCase and possibly leading to more α-synuclein being cleared out, which would be great news for patients: “The increase in [cerebrospinal fluid] α-synuclein could be interpreted as an increase of extracellular export of the protein from the brain parenchyma,” the researchers wrote in 2020.
Importantly, the drug was also found to be safe and well-tolerated by people with Parkinson’s disease, despite the fact that it was being given at much higher doses than are typically found in cough remedies. The next phase of the research is the larger-scale Phase 3 trial that has now been given the green light.
The trial will take place across 10-12 clinical centers in the UK and will involve 330 people with Parkinson’s disease. They will be given ambroxol, or a placebo control, for a period of two years, during which their symptoms will be monitored to see if the treatment is able to slow the progression of the disease.
“Once the ambroxol trial is underway, it will be one of only six Phase 3 trials on public record of potentially disease-modifying drugs in Parkinson’s, worldwide,” said Will Cook, CEO of charity Cure Parkinson’s, which is helping to fund the research.
“This trial is a big step forward in the search to find new treatments for Parkinson’s.”