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Towards a clinical trial to assess the ability of a probiotic bacterium to protect against α-synuclein aggregation in Parkinson’s

This was the topic for our first ever online ERIG meeting, held on Saturday 30th May at 11:00 and attended by 25 members. Talks were given by Drs Maria Doitsidou and David Breen. Maria had given an ERIG talk four years ago about her work using a nematode worm model to study Parkinson’s. Her work has gone well and she had a major publication in January showing that the aggregation of α-synuclein in her model could be slowed down by the actions of bacteria present in a commercially available probiotic. Maria was preparing a major funding application to investigate whether this approach could be applied to Parkinson’s itself. The proposal included a plan for a small clinical trial in Edinburgh to be run by David Breen. Maria and David were keen to tell us about these plans and get input from local people affected by Parkinson’s about the proposed clinical trial.

The meeting began with a slide presentation by Maria that summarised the recent excellent progress with her nematode model, which had demonstrated the ability of the gut bacterium, Bacillus subtilis, to slow down the accumulation of α-synuclein aggregates. She then described how she planned to go on to study the mechanism of the interaction between the gut microbiome and Parkinson’s in her nematode model, but also in a mouse model and in People with Parkinson’s (PwPs) themselves. There followed a lively discussion with an enthusiastic audience about how she thought that the actions of specific gut bacteria could affect the development and progression of such a complex neurological disorder.

A pdf of Maria’s talk can be viewed by clicking here: Doitsidou talk 2020.pdf 

David Breen then outlined the objectives and plans for the proposed clinical trial. Despite realising that the more advanced stage of their Parkinson’s would likely exclude some members from the trial, there was unanimous support amongst the PwPs present for the trial. Concern about the feasibility of conducting a trial during the current Covid-19 pandemic was raised, but David assured the audience that the trial protocol would be “Covid-19 proofed”. He explained that this was a phase 2 trial with the specific limited objectives of assessing the tolerability to daily doses of the B. subtilis probiotic, determining its persistence in the gut and any associated changes in the gut microbiome, and identifying any changes in a variety of blood-based markers relevant to the postulated mechanism of action of the bacterium in affecting the aggregation of α-synuclein. If the trial had a clear positive outcome, then the result could be used to make a very strong case for a larger and longer multi-centre phase 3 trial to investigate the ability of the B. subtilis probiotic to act as a disease modifier for the motor and non-motor symptoms of Parkinson’s. There was extensive discussion about the exclusion criteria for the trial, specifically about the heterogeneous nature of the symptoms experienced by PwPs and whether this would complicate the analysis of results. David stressed that the exclusion criteria and design of such a medium-sized trial had to be rigorous for reliable outcomes to be obtained.

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