Metabolic Agent Vutiglabridin Improves Motor Scores in Early-Stage Study of Parkinson Disease

A phase 2a trial of vutiglabridin, a novel paraoxonase activator, found that patients with early-stage Parkinson disease (PD) who received an 800 mg daily dose had significantly less motor symptom worsening over 24 weeks than those who received placebo. Researchers presented the late-breaking results at the 2026 International Congress of Parkinson's Disease and Movement Disorders (MDS Congress) in Seoul, South Korea.¹

“Treatment with 800 mg vutiglabridin significantly improved MDS-UPDRS part III score in early Parkinson's disease patients as compared with placebo, with a favorable safety profile,” concluded Joong-Seok Kim, MD, professor and head of the department of neurology at the Catholic University of Korea, and colleagues.

The multicenter, double-blind, randomized, placebo-controlled trial (NCT06329141) enrolled patients with newly diagnosed Parkinson's disease across 9 sites in South Korea, randomly assigning them 1:1:1 to daily oral doses of 400 mg or 800 mg vutiglabridin or placebo for 24 weeks, followed by a 4-week washout period. The primary endpoint was change from baseline to week 24 in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III score.^1,2

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Secondary endpoints included MDS-UPDRS score changes at other timepoints, the Non-Motor Symptom Scale, and the Clinical Global Impression of Change, alongside striatal dopamine uptake measured by PET imaging and exploratory analyses of serum neurofilament light chain and PON1 expression and activity.

Of 118 patients screened, 99 were randomized, and 77 were included in the per-protocol efficacy analysis. At 24 weeks, MDS-UPDRS Part III scores changed by -1.37 points in the 400 mg group and -2.83 points in the 800 mg group, both indicating improvement, compared with a change of +0.73 points in the placebo group, indicating worsening. The mean difference between the placebo and 800 mg groups was 3.56 points (P =.03).

The 800 mg group also showed a tendency toward increased serum PON1-specific activity. The abstract did not report specific numeric results for the PET imaging or neurofilament light chain exploratory endpoints. In terms of safety, vutiglabridin was reported as well tolerated, with no drug-related serious adverse events.

Vutiglabridin was initially developed by Glaceum for obesity and metabolic disease before being investigated in PD. Preclinical research published in Molecular Neurodegeneration found that vutiglabridin binds paraoxonase-2 (PON2), a mitochondrial enzyme distinct from PON1, the circulating enzyme whose activity this trial measured as an exploratory biomarker. In MPTP-induced mouse models of PD, vutiglabridin reversed mitochondrial dysfunction, reduced oxidative stress, improved motor function, and protected dopaminergic neurons, effects that were absent in PON2-knockdown mice.³

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REFERENCES
1. Oh Y, Cho JW, Baik JS, Ma HI, Koh SB, Lee PH, Ahn TB, Kim SJ, Kim JS. A multicenter, double-blind, randomized, placebo-controlled, phase 2a clinical trial of vutiglabridin in early-stage Parkinson's disease. Presented at: 2026 International Congress of Parkinson's Disease and Movement Disorders; October 4-8, 2026; Seoul, South Korea. Late-Breaking Abstract LBA22.
2. A randomized, double-blind, placebo-controlled, parallel groups, phase 2a clinical trial to assess the efficacy and safety of vutiglabridin in early Parkinson's disease patients. ClinicalTrials.gov identifier: NCT06329141. Accessed October 6, 2026. https://clinicaltrials.gov/study/NCT06329141
3. An H, Kang S, Shin J, et al. Neurotherapeutic effects of vutiglabridin as a paraoxonase-2 modulator in preclinical models of Parkinson's disease. Mol Neurodegener. 2025;20:110. doi:10.1186/s13024-025-00896-z