Objective: To evaluate the effects of prasinezumab on neuroimaging biomarkers in individuals with early-stage Parkinson’s disease (PD) on stable symptomatic medication.

Background: PD is characterized by the toxic aggregation of α-synuclein and loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Prasinezumab is a monoclonal antibody designed to bind and clear extracellular aggregated α-synuclein.

Method: The Phase IIb PADOVA study (NCT04777331) evaluated the efficacy, safety and pharmacokinetics of prasinezumab in participants with early-stage PD on stable monoamine oxidase type B inhibitor (MAO-Bi) or levodopa monotherapy. Biomarker endpoints included magnetic resonance imaging (MRI) of basal ganglia (putamen and caudate) and SNpc using a T1-weighted neuromelanin (NM)-sensitive sequence as well as R2* relaxometry sensitive to iron deposition at baseline and week 76 at sites where the respective sequences were available.

Results: Of 586 enrolled participants, 194 provided longitudinal NM-MRI scans and 202 provided iron-sensitive MRI scans for analysis based on automated segmentation of regions of interest. In pre-specified analysis of covariance (ANCOVA) models, changes in SNpc NM intensity showed a trend towards increased SNpc NM intensity in the prasinezumab group (adjusted mean change [95% confidence interval]: 0.18 [-0.18, 0.55]), relative to levels in the placebo group (–0.16 [–0.52, 0.20]; p=0.0792). Prasinezumab treatment also showed a trend towards decreased in SNpc iron, relative to the placebo group (–0.06 [–1.33, 0.27] vs. 0.47 [–0.26, 1.21], p=0.1903). This pattern was more pronounced in the putamen (–0.22 [–0.62, 0.18] vs. 0.43 [0.05, 0.82], p=0.0025). Notably, further correlation analysis confirmed links between NM, iron, dopamine transporter-single-photon emission computed tomography and Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale Part III.

Conclusion: Exploratory biomarker analysis of PADOVA suggests that prasinezumab is biologically active. This is supported by imaging biomarkers crucial to PD pathology, suggesting a trend in slowing in the progressive loss of NM signal in SNpc and reduced iron accumulation in the putamen.

This abstract was previously presented at ADPD 2026 on 17–21 March 2026.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/prasinezumabs-impact-on-neuromelanin-and-iron-sensitive-mri-biomarkers-in-parkinsons-disease-findings-from-the-padova-phase-iib-study/