Summary: Ambroxol, an established medication for respiratory conditions, is showing promise as a potential therapy to slow the progression of Parkinson’s disease. New research indicates ambroxol raises levels of the enzyme GCase (glucocerebrosidase), which helps cells clear waste proteins such as alpha-synuclein that accumulate in Parkinson’s.
Source: UCL
Ambroxol is currently prescribed to treat respiratory problems by loosening mucus, easing cough, and reducing inflammation. Recent laboratory and early clinical research suggests it may also influence biological pathways relevant to Parkinson’s disease, making it a candidate for repurposing as a disease-modifying treatment.
Pre-clinical studies led by Professor Anthony Schapira at the UCL Queen Square Institute of Neurology identified ambroxol as a promising compound for Parkinson’s. Those laboratory studies showed ambroxol can increase activity of glucocerebrosidase (GCase), an enzyme that supports the cellular clearance of misfolded proteins, including alpha-synuclein—the protein that aggregates in Parkinson’s and is implicated in neuronal damage.
A Phase 2 clinical trial led by Professor Schapira and carried out at UCL, published in January 2020, tested ambroxol in people living with Parkinson’s. The study demonstrated that ambroxol can cross into the brain and raise levels of GCase. By improving the cell’s ability to remove toxic proteins, ambroxol may reduce the buildup of alpha-synuclein and the cellular stress associated with Parkinson’s progression.
Importantly, the Phase 2 data also showed ambroxol was safe and well tolerated in the participants studied, supporting further investigation in larger, longer trials focused on clinical outcomes and disease progression.
Building on these results, the world-first Phase 3 trial, named ASPro-PD, is being led by Professor Schapira in collaboration with the U.K. charity Cure Parkinson’s and the Van Andel Institute. The Phase 3 trial represents a major step in translating laboratory findings into a rigorous, definitive test of ambroxol as a disease-modifying therapy for Parkinson’s disease.
ASPro-PD will recruit 330 people with Parkinson’s across 10–12 clinical centres in the U.K. The study is placebo-controlled and participants will receive ambroxol or placebo for two years. Trial investigators will assess whether ambroxol slows Parkinson’s progression using clinical rating scales that evaluate movement, function, and quality of life, alongside other relevant outcome measures. Preparations for participant recruitment have already begun.
Professor Schapira commented, “I am delighted to be leading this exciting project. 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. The study design reflects valuable input from people with Parkinson’s, leaders in the field, trial design and statistics experts from the UCL Comprehensive Clinical Trials Unit (CCTU), the MHRA and a consortium of funders led by Cure Parkinson’s, all operating as an effective team to ensure we have reached this stage. We look forward to working with all these groups to ensure successful completion of the study.”
Following the Phase 2 results from Professor Schapira’s team, the international Linked Clinical Trials (iLCT) program prioritized ambroxol for further study. The iLCT initiative, created and operated by Cure Parkinson’s and the Van Andel Institute, aims to accelerate development of disease-modifying therapies for Parkinson’s by testing promising drugs that already have substantial safety data or regulatory approval for other indications.
Will Cook, CEO of Cure Parkinson’s, said, “This trial is a big step forward in the search to find new treatments for Parkinson’s. 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. We at Cure Parkinson’s are working hard—through our efforts within the iLCT program and via fundraising—to increase this number significantly in the next few years, to accelerate our progress towards a cure for Parkinson’s.”
About this Parkinson’s disease and neuropharmacology research news
Author: Poppy Danby
Source: UCL
Contact: Poppy Danby – UCL
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