AD/PD 2026 | Repurposing ambroxol for the treatment of synucleinopathies
Stephen Pasternak, MD CM, PhD, FRCPC, Western University, London, Canada, discusses the rationale for repurposing ambroxol in Parkinson’s disease and related synucleinopathies. Originally identified in Gaucher disease research, ambroxol enhances glucocerebrosidase activity, a pathway linked to GBA1 mutations and increased risk of neurodegeneration, with early studies suggesting potential cognitive and motor benefits. This interview took place at the AD/PD™ 2026 International Conference on Alzheimer’s and Parkinson’s Diseases in Copenhagen, Denmark.
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Transcript
So, ambroxol is an over-the-counter cough medication that’s available across almost the entire world, but not in Canada or the United States. It has a long safety record, including safety in high doses in pregnant women in Europe. It came to attention at the Hospital for Sick Children in Toronto in something called the high-throughput screen where people were looking for drugs. In this case, they were looking for drugs that stabilized an enzyme for Gaucher disease...
So, ambroxol is an over-the-counter cough medication that’s available across almost the entire world, but not in Canada or the United States. It has a long safety record, including safety in high doses in pregnant women in Europe. It came to attention at the Hospital for Sick Children in Toronto in something called the high-throughput screen where people were looking for drugs. In this case, they were looking for drugs that stabilized an enzyme for Gaucher disease. So Gaucher disease is a disease where you are missing a key enzyme in a compartment called the lysosome, which is a normal recycling digestive part of the cell. And the substrate builds up and kills the cell. So it’s a terrible degenerative disease in a multi-system, often including the brain. So if you have two mutations in this enzyme, GBA1, or glucocerebrosidase, then you have Gaucher disease, again, this horrible pediatric disease. But if you’re a carrier, it turns out that this is the highest or the largest risk factor for synucleinopathy. So Parkinson’s disease, Parkinson’s disease dementia, and Lewy body dementia. And so this actually was found when I was a postdoc at SickKids quite a while ago. So again, being an adult neurologist, I said, oh my gosh, we have to try this in Parkinson’s disease. So this drug, at the time we started this, really there wasn’t a lot of evidence, but a small number of patients with Gaucher disease had been treated in a small cohort in Japan. Right now, again, so the cohort in Japan is published. And so there was actually improvement in cognition and seizure frequency in Gaucher disease patients. And there are now probably 180 patients in basically case reports who seem to be doing better on ambroxol, and this is widely used off-label. While our trial was ongoing, Dr Schapira in England looked at 18 patients with Parkinson’s disease, some with GBA mutations and some without, and found that there probably was an improvement in motor function in these patients. So it’s an open-label study, so it was very encouraging, but it wasn’t conclusive.
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Disclosures
I am a shareholder of Zywie Bio LLC (Princeton NJ) and have recieved grant support from them. I have received consultants’ fees from Liley and Eisai. I have patients in many clinical trials. AriBio and Novartis are the recent ones that I am site PI on.
