A liver drug could be used to slow down the progression of Parkinson’s disease as it joins the world’s largest trial of treatments for the condition.
This comes after researchers at the University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust discovered ursodeoxycholic acid (UDCA) as having considerable promise to improve mitochondrial function, known as the cell’s power plants, in Parkinson’s disease and by doing so slow the progression of this currently relentlessly progressive disease.
UDCA was identified as a potential new avenue for treatment of Parkinson’s following groundbreaking University of Sheffield-led research which screened an entire drug library in Parkinson’s patient tissue samples for the first time. The initial drug screen was funded by Parkinson’s UK.
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. This clinical trial is sponsored by University College London (UCL) and is funded by the Efficacy and Mechanism Evaluation (EME) Programme, an MRC and NIHR partnership (NIHR160829), Cure Parkinson’s, The Michael J Fox Foundation, Parkinson’s UK, The John Black Charitable Foundation, The Gatsby Charitable Foundation and Van Andel Institute.
The loss of mitochondrial 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.
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 Parkinson’s patients in an early-stage clinical trial, the UP study, which was co-funded by the Jon Moulton Charity Trust and Cure Parkinson’s. It was also strongly supported by the NIHR Biomedical Research Centre Sheffield.
However, large-scale testing is now needed to assess effectiveness further.
The drug was selected for inclusion in the EJS ACT-PD trial following an extensive review of hundreds of potential therapies by scientific experts and people with Parkinson’s, identifying those with the strongest evidence for slowing Parkinson’s disease progression.
As the UDCA treatment has a different dosing regimen to the two active treatments already being tested (telmisartan and terazosin), participants who join the trial from now on will be randomly assigned into one of five treatment groups (the three active treatments UDCA, telmisartan and terazosin and two placebo groups) depending on which they are eligible for.
The trial, which is being led nationally by researchers at University College London (UCL) and Newcastle University and managed by the UCL Innovative Clinical Trials Unit (InCTU), will recruit 2,000 participants from across 40 NHS hospital sites. Neither participants nor the study team know which treatments or placebo have been assigned whilst the trial is taking place.
The addition of UDCA to the EJS ACT-PD trial is also a particularly significant achievement for the Sheffield team as it is rare for an academically led drug discovery programme to progress from initial laboratory discovery through a phase 2 trial with a novel design to a definitive phase 3 trial.
Professor Oliver Bandmann, Professor of Movement Disorders Neurology at the University of Sheffield and Honorary Consultant Neurologist at Sheffield Teaching Hospitals NHS Foundation Trust, 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.”
He added: “Having led both the original drug discovery programme and the UP study (together with Prof 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 Newcastle University.
“This is an excellent example of how discoveries made in patient-derived tissue can progress through early clinical testing towards large-scale trials, with the ultimate aim of developing treatments that slow or stop the progression of Parkinson’s disease.”
Professor Camille Carroll,Professor of Clinical Neuroscience at Newcastle University and 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.”
