Cough medicine offers hope of new treatment to slow the progression of Parkinsonâs disease
10 January 2023
Following promising results reported at Phase 2 in 2020, a large-scale Phase 3 clinical trial of ambroxol, a drug currently in use to treat respiratory conditions, will start in early 2023.
The ASPro-PD trial is a world-first Phase 3 trial aimed at establishing ambroxolâs potential to slow the progression of Parkinsonâs. Following eight years of work with the Parkinsonâs community, driven by UK charity Cure Parkinsonâs in partnership with Van Andel Institute and the John Black Charitable Foundation, this ÂŁ5.5 million trial will investigate the ability of ambroxol to slow the progress of Parkinsonâs.
This ground-breaking trial, led by Professor Anthony Schapira at University College London (MyAV·¶), will involve 330 people with Parkinsonâs across 10-12 clinical centres in the UK. The trial is placebo controlled and participants will take the drug or placebo for two years. The effectiveness of ambroxol will be measured by its ability to slow the progression of Parkinsonâs using a clinical scale including quality of life and movement. Preparations for recruitment of trial participants have already started.
Ambroxol is one of the drugs prioritised by the International Linked Clinical Trials (iLCT) programme, created and operated by Cure Parkinsonâs and Van Andel Institute. The programmeâs mission is to slow, stop and reverse the progression of Parkinsonâs. It aims to significantly reduce the time to bring disease-modifying treatments to clinic for the Parkinsonâs community by testing promising drugs that already have extensive safety data and, in some cases, have been approved by regulators for other medical conditions.
About ambroxol
Ambroxol is a medication that is commonly used in Europe as a treatment for respiratory diseases. It promotes the clearance of mucus, eases coughing and has anti-inflammatory properties.
After reviewing pre-clinical laboratory data from Professor Schapiraâs group at MyAV·¶, a committee of experts brought together by Cure Parkinson's in 2014 prioritised ambroxol for further investigation agreeing that it has the potential to slow or stop the progression of Parkinsonâs. This was based on the demonstration that ambroxol could increase the removal of alpha-synuclein, a protein that builds up in Parkinsonâs and is thought to be important in its cause.
Results of the Phase 2 clinical trial, which tested ambroxol in people with Parkinsonâs were published in January 2020 in The Journal of the American Medical Association (JAMA) Neurology. The data showed that ambroxol was able to effectively reach the brain and increase levels of a protein known as GCase (glucocerebrosidase). GCase allows cells to remove waste proteins, including alpha-synuclein, more effectively.
In addition, the Phase 2 trial showed that ambroxol was safe for people with Parkinsonâs and was well tolerated. This trial was funded and supported by Cure Parkinsonâs, Van Andel Institute and the John Black Charitable Foundation.
Funding
This trial will cost ÂŁ5.5 million, which is being funded by Cure Parkinsonâs alongside its strategic partners, Van Andel Institute and the John Black Charitable Foundation (JBCF), and by the Parkinsonâs Virtual Biotech, the drug discovery and development arm of Parkinson's UK. Cure Parkinsonâs is committing to fund ÂŁ2.2 million of the total cost, with the other funders contributing ÂŁ1.1 million each.
Taking Part
Anyone interested in taking part in the ambroxol trial is encouraged to enrol in âPD Frontlineâ, a remote study offering online genetic testing for people with Parkinsonâs. This can be done now and will help with recruiting people to the ASPro-PD trial, as well as others.Â
Will Cook, CEO of Cure Parkinsonâs, said:Â âThis trial is a big step forward in the search to find new treatments for Parkinsonâs. 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 Parkinsonâs, worldwide. We at Cure Parkinsonâs are working hard - through our efforts within the iLCT programme and in our fundraising efforts â to increase this number significantly in the next few years, to accelerate our progress towards a cure for Parkinsonâs.â
Professor Anthony Schapira, Head of Department of Clinical and Movement Neurosciences at MyAV·¶ Queen Square Institute of Neurology, University College London Hospitals NHS Foundation Trust (MyAV·¶H) and the Royal Free London NHS Hospital Trust, and the Chief Principal Investigator of ASPro-PD said:Â âI am delighted to be leading this exciting project. This will be the first time a drug specifically applied to a genetic cause of Parkinsonâs 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 is the result of valuable input from people with Parkinsonâs, leaders in the field of Parkinsonâs, trial design and statistics from the MyAV·¶ CCTU, the MHRA and a consortium of funders led by Cure Parkinsonâs, 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.â
Peter A. Jones, Ph.D., D.Sc. (hon), Chief Scientific Officer at Van Andel Institute said:Â âFor a decade, the International Linked Clinical Trials programme has worked tirelessly to move promising potential therapies for Parkinsonâs into clinical trials. Van Andel Institute is thrilled to continue partnering with Cure Parkinsonâs on this vital initiative and we look forward to a bright future in which slowing or stopping disease progression isnât a dream â it is a reality.â
Darren Moore, Ph.D., Chair of the Department of Neurodegenerative Science at Van Andel Institute and a member of the International Linked Clinical Trials Committee, added: âThe movement of ambroxol into a Phase 3 clinical trial is a leap forward in our pursuit of treatments that slow or stop Parkinsonâs progression. Ambroxol has shown promising results in a Phase 2 trial and, because it is a commonly used respiratory medication, it has already gone through rigorous safety testing. Very few potential treatments for Parkinsonâs have reached Phase 3 trials, which makes todayâs news that much more exciting. The trial is a testament to the power of collaboration spurred on by the International Linked Clinical Trials initiative.â
Professor David Dexter, Associate Director of Research at Parkinsonâs UK said:Â âWeâre really pleased that the Virtual Biotech is co-funding this new trial with Cure Parkinsonâs and their strategic partners. People with Parkinsonâs desperately need new and better treatments, and if this trial is a success, ambroxol has the potential to be available in years and not decades. The Parkinsonâs Virtual Biotech is built on a foundation of international collaboration, investing in the most promising drug discovery and development projects. We know that weâll get results for the global Parkinsonâs community faster by collaborating, not competing. By working together, we can find a cure.â
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Image
- Parkinson's disease. 3D illustration showing neurons containing Lewy bodies small red spheres which are deposits of proteins (alpha-synuclein) accumulated in the brain cells. Credit:Â Â on iStock