The Ambroxol Trial - The facts Why is Ambroxol being trialled and why is this drug an important target? Ambroxol is a drug which has been commonly used as an anti-mucolytic respiratory medicine since the 1980’s. Recent studies in Parkinson’s models and cells extracted from patients indicate that the drug may help to reduce an unwanted build-up of the toxic protein alpha-synuclein in neurons, which is a defining aspect of Parkinson’s. Why are we investigating whether Ambroxol might be a beneficial treatment in Parkinson’s? People with Parkinson's disease (PD) with the single GBA gene mutation are predisposed to develop movement impairment at a younger age, have a higher degree of cognitive dysfunction and undergo more rapid disease progression. GBA mutations cause dysfunction in the naturally occuring enzyme protein glucocerebrosidase (GCase), which can lead to build-up of the protein alpha-synuclein. Ambroxol has been shown to improve the function of glucocerebrosidase in neurons, which helps reduce the build-up of alpha-synuclein. If we can reduce these aggregated clumps of alpha-synuclein in neurons, we hope to slow the progression of Parkinson’s. Who will be involved in this study? This is the first trial to be funded through The Cure Parkinson’s Trust and the Van Andel Research Institute's shared funding initiative. The study, to be carried out in 20 people with the genetic form of PD, over 24 months and will be led by Professor Anthony Schapira at the Royal Free Hospital. Why do researchers think this drug is a potential treatment to slow, stop or reverse Parkinson’s? It is felt likely that removal of excess abnormal alpha-synuclein from neurons may improve stability and motor ability in people with Parkinson’s. By using a drug which has shown to reduce the build-up of alpha-synuclein, and which also has a long and well-understood safety record, we hope we might have a candidate for long term use that will reduce or even halt the progression of the disease. Prior to undertaking a large trial to investigate this potential efficacy we need to learn a little more about Ambroxol in PD patients and whilst this small trial may give some indications of its ability to improve motor activity quality of life of patients, its main aim is to gain knowledge about its safety and ability to penetrate the blood brain barrier at dose levels that are close to those that have been shown to be safe to date. A number of biomarkers will be examined to help to characterise the potential beneficial action of the drug. What do we hope will be the result of this important work? This pilot study will allow us to clarify some of the beneficial characteristics of the drug in Parkinson’s – determining dose, finding out exactly how much of an effect the drug has, and in what situations the effect of the drug is most prominent.This study will form the basis for the design of a larger trial. As Ambroxol is already approved as a drug to treat another condition in some countries, if a larger trial is successful, this drug would be readily accessible and could be seen as a treatment to slow down Parkinson’s within a short timeframe. This would have a huge impact on the lives of many people living with Parkinson’s today. ** Professor Anthony Schapira is researching further therapies targeted to the GBA gene mutation to understand more about the pathways of GCase and its connection to alpha-synuclein. CPT continues to support and follow Professor Schapira's work in this exciting research area.