UDCA (UP study)

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Thomas Payne, Oliver Bandmann and colleagues at the University of Sheffield, with Tom Foltynie and colleagues at University College London Hospitals. Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust. Cure Parkinson's says it funded the study; the registry lists the JP Moulton Charitable Foundation as a collaborator. Published in Movement Disorders, 2023.

What happened

Mitochondria are the cell's power plants, and a defect in them was found in the Parkinson's brain (landmark 11). The gene parkin, when mutated, causes early-onset Parkinson's with faulty mitochondria (landmark 12).

• Origin. In 2013 Mortiboys, Aasly and Bandmann (Brain) screened a 2,000-compound library on skin cells from people with parkin mutations. Fifteen compounds repaired mitochondrial function in cells from additional patients, and two were studied further. Those two were not licensed drugs, but UDCA, a chemically related licensed bile acid, rescued function to a similar extent, and both also worked in LRRK2 (G2019S) patient cells. The paper reports a Parkin-deficient neuronal model; I did not check the fly and rat work.
• Trial. Double-blind, placebo-controlled Phase 2. 30 people diagnosed within 3 years (the registry counts 31 enrolled), randomised 2:1 to UDCA 30 mg per kg daily or placebo for 48 weeks (UK; NCT03840005; started December 2018, last visit May 2021).
• Safety (main goal). Safe and well tolerated; only mild, passing gut side effects were more common on UDCA.
• Target engagement. Phosphorus magnetic resonance spectroscopy (31P-MRS, a scan that reads energy chemicals) showed higher Gibbs free energy and inorganic phosphate in the midbrain on UDCA than placebo, which the authors read as improved ATP (energy currency) breakdown.
• Motor measures. The clinician-rated MDS-UPDRS Part III showed no difference between groups. Wearable gait sensors suggested faster stepping (cadence) and other gait gains on UDCA. These were exploratory.

Why it moved us toward a cure

It is the first mitochondrial-rescue drug to show a hint of working on its target in the living Parkinson's brain, via a repurposed, cheap drug. This is the first step needed before a large efficacy trial; an earlier high-dose coenzyme Q10 trial had failed (QE3). Cure Parkinson's says a larger trial is being worked on; I found no registered one.

Outcome

Open. A safety and target-engagement study only. Efficacy remains unknown, and a ClinicalTrials.gov search (19 Oct 2026) shows no larger UDCA Parkinson's trial (only a 5-person Minnesota Phase 1, NCT02967250).

Sources

• Payne et al., Mov Disord 2023;38(8):1493–1502, DOI 10.1002/mds.29450 (PMID 37246815)
• Cure Parkinson's, UP study page (author discloses he is Cure Parkinson's Director of Research)
• ClinicalTrials.gov NCT03840005 (API, 19 Oct 2026)
• Mortiboys, Aasly, Bandmann, Brain 2013;136:3038–3050, DOI 10.1093/brain/awt224, PMID 24000005
• Not yet verified: numeric 31P-MRS values and the full text (abstract read); the BMJ Open 2020 protocol (cited earlier, not re-checked); the Minnesota study's results (Cure Parkinson's page only); the Sheffield-side plan for a larger trial.