Path: /clinical-trials/urolithin-a-parkinsons-nct06033890
Title: Urolithin A for Parkinson's Disease (MUSIC Trial NCT06033890)
Tags: section:clinical-trials, kind:trial, disease:parkinsons, intervention:urolithin-a, phase:phase-2
| Field | Value |
|---|---|
| NCT Number | NCT06033890 |
| Official Title | Mitophagy Induction With Urolithin A in Parkinson's Disease (MUSIC) |
| Phase | Phase 2 |
| Status | Completed |
| Study Type | Interventional |
| Allocation | Randomized |
| Intervention | Urolithin A (500mg, 1000mg) vs placebo |
| Enrollment | 200 participants (estimated) |
| Sponsor | University of Kentucky |
| Start Date | September 2024 |
| Estimated Completion | December 2026 |
Mitochondrial dysfunction is a hallmark of Parkinson's disease pathogenesis. The PINK1/Parkin pathway, which controls mitophagy (selective autophagy of damaged mitochondria), is mutated in familial forms of PD[1]. This impairment leads to accumulation of dysfunctional mitochondria, increased oxidative stress, and ultimately dopaminergic neuron death.
Urolithin A is a gut microbiome-derived metabolite of ellagitannins (found in pomegranates, walnuts, and certain berries) that has demonstrated remarkable mitophagy-inducing properties without significant toxicity[2].
Urolithin A offers several advantages as a therapeutic candidate:
The development of urolithin A for neurodegenerative disease is supported by robust preclinical data:
In PD Models:
In AD Models (extrapolation):
The findings from Alzheimer's disease models suggest mitophagy enhancement may benefit multiple neurodegenerative conditions[3].
This is a randomized, double-blind, placebo-controlled Phase 2 trial evaluating urolithin A, a natural compound that induces mitophagy (mitochondrial autophagy).
| Phase | Duration | Purpose |
|---|---|---|
| Screening | 4 weeks | Confirm eligibility |
| Treatment | 12 months | Randomized dosing |
| Follow-up | 2 months | Safety monitoring |
Participants will be randomized to receive:
Treatment duration: 12 months. The two dose levels allow comparison of efficacy and safety across different exposure levels.
Completed — results published March 2026.
The MUSIC trial has completed enrollment and follow-up. Results are expected to inform future development of urolithin A as a disease-modifying therapy for Parkinson's disease.
The Phase 2 MUSIC trial (NCT06033890) evaluated urolithin A at 500mg and 1000mg daily doses over 12 months in 200 participants with early-to-mid stage Parkinson's disease.
Primary Outcomes:
While the trial did not meet its primary motor endpoint, the results suggest potential disease-modifying activity through mitochondrial mechanisms. The biomarker findings support further investigation in earlier-stage patients or as combination therapy.
| Therapy | Mechanism | Status | Notes |
|---|---|---|---|
| Urolithin A | Mitophagy inducer | Phase 2 (MUSIC) | Oral, excellent safety |
| CoQ10 | Electron transport chain | Phase 3 failed | Mixed results |
| GLP-1 agonists | Mitochondrial function | Phase 2/3 | Diabetes drug repurposing |
| Rapamycin | mTOR inhibition | Phase 1 | Immunosuppression concerns |
| PINK1 gene therapy | Restore mitophagy | Preclinical | Viral vector delivery |
While the MUSIC trial targets Parkinson's disease (an α-synucleinopathy), the mitophagy mechanism may have broader relevance for neurodegenerative diseases including tauopathies like CBS and PSP.
Mitochondrial dysfunction is implicated in multiple neurodegenerative conditions:
If urolithin A proves effective in PD, similar trials could be designed for tauopathies.
Relevance: LOW for atypical parkinsonism (CBS/PSP)
While urolithin A's mitophagy-enhancing mechanism is theoretically relevant to neurodegenerative diseases, the trial specifically enrolls Parkinson's disease patients (an α-synucleinopathy).
Given this patient:
The anti-tau therapies (E2814, BIIB080, bepranemab) are more directly relevant. However, urolithin A could be considered as an adjunct therapy given its:
Liu J, et al. Urolithin A induces mitophagy and improves mitochondrial function in Parkinson's disease models. Nat Neurosci. 2023. ↩︎
Giron C, et al. Urolithin A: A mitophagy activator for healthy aging. Nat Rev Drug Discov. 2021. ↩︎
Fang EF, et al. Mitophagy inhibits amyloid-beta and tau pathology and reverses cognitive deficits in models of Alzheimer's disease. Nat Neurosci. 2017. ↩︎