What is the evidence for ambroxol as a potential treatment for Parkinson’s?
In 2009, researchers were searching for potential ways to treat Gaucher disease, which is caused by a deficiency of the enzyme GCase. The researchers were looking for drugs to help increase levels of GCase in cells, in the hope that boosting GCase activity will help cells improve their waste clearance, thereby making them healthier. They tested a library of over 1,000 existing drugs to see if any of these drugs could increase GCase activity. They found that, out of all the compounds screened, ambroxol was a potent GCase enhancer, and this is where the ambroxol and Parkinson’s story began.
Making the case for GCase
Professor Anthony Schapira at University College London and the Royal Free Hospital instigated further research into this promising research pathway. His team found that when skin cell samples taken from people with Parkinson’s were treated with ambroxol, the level of GCase activity in these cells increased.
The phase 2 trial of ambroxol – AIM-PD:
Cure Parkinson’s, Van Andel Institute and the John Black Foundation funded and supported the small phase 2 clinical trial of ambroxol in people with Parkinson’s called AIM-PD, which was led by Professor Schapira. This ran from January 2017 to April 2018 and its purpose was to lay the foundations for larger trials of ambroxol by answering fundamental questions about its safety, suitability and effectiveness as a potential treatment for people with Parkinson’s.
The findings from the trial were by no means conclusive because they came from a small ‘proof-of-concept’ study testing simple biochemical changes in the 17 trial participants. Nevertheless, the results added to the evidence that GCase enhancement is a really promising research target to find treatments to slow, stop or reverse the progression of Parkinson’s.
To get to this stage, a wide range of people from the Parkinson’s community have been involved: through consultation, early laboratory based research and clinical trial work, the trial has already had input from neuroscientists and neurologists, medical regulators and people with Parkinson’s. The phase 3 trial of ambroxol called ‘ASPro – PD’ is in set-up. This trial, it is hoped, will determine if ambroxol can slow or stop the progression of Parkinson’s.
If the ASPro-PD clinical trial proves that ambroxol does indeed slow the progression of Parkinson’s, the urgent focus of everyone involved will be to ensure that the drug reaches people with Parkinson’s as quickly as possible, working with the pharmaceutical industry and regulators to make this happen. Time is of the essence; provisional work on this has already started.
The genetics of Parkinson’s has provided us with insights into the underlying biology of the condition; we now understand more about the biological processes associated with certain genetic risk factors, and treatments are being developed to target these aspects of the condition. Importantly, these new potential treatments are being tested in people with Parkinson’s to see if they have beneficial effects for the wider Parkinson’s community, not just for individuals carrying certain genetic risk factors. Recently, there has been increasing evidence supporting this; some of the biological pathways associated with genetic variations appear to be abnormal in people with Parkinson’s who do not carry genetic mutations.
PD Frontline is an online genetic study which aims to put people with Parkinson’s at the forefront of ongoing research. For the first time, drugs that protect against or slow down the progression of Parkinson’s are a real possibility, and many such drugs are targeted at specific genes which we know influence the development of Parkinson’s, such as the GBA-1 gene.
Crucially, to test whether these drugs work, we need to identify people with variations in specific genes who can then take part in clinical trials. PD Frontline tests for two genetic risk factors for Parkinson’s; these are the GBA1 gene and the LRRK2 gene.