Making the case for GCase
Researchers have been looking for drugs that 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; and if cells are healthier, this might then slow down the progression of Parkinson’s.
Professor Anthony Schapira at University College London and the Royal Free Hospital instigated further research into this promising biological pathway. His team found that treating skin cell samples from people with Parkinson’s with ambroxol, increased their GCase level of activity.
The previous research
The phase 2 trial of ambroxol – the AIM-PD trial:
Cure Parkinson’s, together with Van Andel Institute and the John Black Charitable Foundation, funded a small phase 2 clinical trial of ambroxol in people with Parkinson’s (called AIM-PD), 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 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 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 course of Parkinson’s.
The next steps
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 genetic risk factors, and experimental treatments have been developed to target them. These novel treatments are being clinically tested to see if they will have beneficial effects not just for individuals carrying certain genetic risk factors, but also for the wider Parkinson’s community. Recently, there has been increasing evidence supporting this; some of the biological pathways associated with these genetic variations appear to also be abnormal in people with Parkinson’s who do not carry the genetic variation.
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.
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 GBA1 and LRRK2.
Cure Parkinson’s is now working hard with researchers to robustly assess the potential of ambroxol as a future treatment for Parkinson’s. We are also keeping abreast of another clinical trial of ambroxol in Parkinson’s that is underway in Canada, as well as several research programmes investigating other ways to target GCase and its actions.
The evidence for ambroxol and GCase enhancers continues to build and Cure Parkinson’s is at the forefront of driving this into clinical practice for the treatment of people with Parkinson’s.