An existing liver drug discovered by researchers at Sheffield Teaching Hospitals NHS Foundation Trust and the University of Sheffield as a key target to slow or halt Parkinson’s is being included in the world's largest trial of treatments for the condition. 

Ursodeoxycholic acid (UDCA) was identified as a potential new treatment for Parkinson's following research by the University of Sheffield and Sheffield Teaching Hospitals which screened an entire drug library in tissue samples from people with Parkinson’s for the first time. The initial drug screen was funded by Parkinson’s UK. 

The drug has considerable promise to improve mitochondria function, known as the cell’s power plants, in Parkinson’s disease. The loss of mitochondria function in dopamine-producing nerve cells in the movement-controlling area of the brain is believed to play an important role in the progression of Parkinson's. By protecting these nerve cells from cellular malfunction, researchers believe UDCA can play a key role in slowing Parkinson's progression.  

It is now the third of a new wave of treatments with disease-modifying potential to be tested in parallel against a placebo in the Edmond J Safra Accelerating Clinical Trials in Parkinson’s Disease (EJS ACT-PD) trial, funded by the National Institute for Health and Care Research (NIHR) and a consortium of national and international charities. 

Milestone in search for Parkinson's treatments

The inclusion of the UDCA drug into the innovative multi-drug EJS ACT-PD trial marks an important milestone for the platform which aims to speed up the search for effective treatments for Parkinson's by testing more drugs faster and more efficiently than ever before. Up until now, there have been two active treatment arms (telmisartan and terazosin), with UDCA joining as the third active treatment arm. 

UDCA has been used to treat certain liver conditions for over 30 years and was shown to be safe and effective for use in people with Parkinson's in an early-stage clinical trial known as the UP study, which was co-funded by the Jon Moulton Charity Trust and Cure Parkinson’s and also strongly supported by the NIHR Biomedical Research Centre (BRC) Sheffield. However, large-scale testing is now needed to assess effectiveness further. 

The EJS ACT-PD trial is being led nationally by University College London (UCL) and Newcastle University. It will recruit 2,000 participants from across 40 NHS hospital sites including Sheffield. Neither participants nor the study team will know which treatments or placebo have been assigned whilst the trial is taking place. 

Sheffield leads the way

Professor Oliver Bandmann, Honorary Consultant Neurologist at Sheffield Teaching Hospitals NHS Foundation Trust and Professor of Movement Disorders Neurology at the University of Sheffield, led the drug's development and will act as co-lead of the UDCA treatment arm in the EJS ACT-PD trial together with Professor Tom Foltynie at UCL and Professor Camille Carroll at Newcastle University. 

Professor Bandmann said:  

“The launch of the UDCA arm of EJS ACT-PD represents a major milestone in a programme of translational Parkinson’s research jointly led by the University of Sheffield and Sheffield Teaching Hospitals and the NIHR Biomedical Research Centre (BRC) Sheffield over more than a decade.  

"Our research began with the first systematic screening of an entire library of compounds in tissue from people with Parkinson’s disease at the Sheffield Institute for Translational Neuroscience (SITraN). This identified UDCA, an existing medication for liver disease, as a promising candidate for protecting nerve cells by improving mitochondrial function. 

"We subsequently took UDCA from the laboratory into a proof-of-concept clinical trial, the UP study, which demonstrated that the drug was safe and well tolerated in people with Parkinson’s disease and provided encouraging evidence of its effects on brain energy metabolism.” 

"Having led both the original drug discovery programme and the UP study (together with Professor Foltynie from UCL), I am particularly excited to now co-lead the definitive phase 3 evaluation of UDCA within EJS ACT-PD together with colleagues from UCL and the University of Newcastle.” 

Professor Camille Carroll, Professor of Clinical Neuroscience at Newcastle University and the NIHR Newcastle BRC, said:  

“Bringing UDCA into the trial as a third treatment arm is exactly what our flexible design was built for: we can add promising drugs as the evidence for them emerges, within the same trial infrastructure, and so test more treatments more quickly. It is a great credit to the Sheffield team that a drug first identified in tissue from people with Parkinson’s has now reached a large-scale trial. 

“We are again very grateful to the people with Parkinson’s and care partners who helped us choose which drugs to test and how the trial should run. Thanks to their input, more people with Parkinson’s across the UK now have the opportunity to take part in testing a drug that may slow the progression of the condition.” 

Parkinson's patient Gary Moran, who took part in the phase 2 UP study, shared his experience of taking part in the drug's clinical development: 

"Having been diagnosed with Parkinson’s I joined the phase 2 Up Study with Professor Bandmann and his team at Sheffield Teaching Hospitals. From the very beginning Professor Bandmann and his team were very professional, provided everyone with constant support, and everyone had regular updates throughout the duration of the study. Over the study period I felt very comfortable taking the medication and believe that it helped with my symptoms at the time." 

About the EJS ACT-PD Third Treatment Arm  

Participants who join the EJS-ACT PD trial from now on will be randomly assigned to one of the five treatment groups depending on which they are eligible for.  

• Group A: a once-a-day placebo capsule (or dummy drug) plus their usual Parkinson’s care  

• Group B: Telmisartan (40mg per day taken once-a-day) plus their usual Parkinson’s care 

• Group C: Terazosin (5mg per day taken once-a-day) plus their usual Parkinson’s care 

• Group D: UDCA (1,500mg to 2500mg per day) split between 3, 4 or 5 tablets taken at three separate times during the day plus their usual Parkinson’s care 

• Group E: 3, 4 or 5 placebo tablets (or dummy drug) taken at three separate times during the day plus their usual Parkinson’s care. 

Further details can be found here. 

The NIHR funds, enables and delivers world-leading health and social care research that improves people's health and wellbeing and promotes economic growth.

NIHR Biomedical Research Centres (BRCs) are collaborations between NHS organisations and universities. They bring together academics and clinicians to translate scientific discoveries into potential new treatments, diagnostics and technologies.