Reproducibility of PD patient-specific midbrain organoid data for in vitro disease modeling

Summary

Midbrain organoids are advanced in vitro cellular models for disease modeling. They have been used successfully over the past decade for Parkinson's disease (PD) research and drug development. The three-dimensional structure and multicellular composition allow disease research under more physiological conditions than is possible with conventional 2D cellular models. However, there are concerns in the field regarding the organoid batch-to-batch variability and thus the reproducibility of the results. In this manuscript, we generate multiple independent midbrain organoid batches derived from healthy individuals or glucocerebrosidase (GBA)-N370S mutation-carrying PD patients to evaluate the reproducibility of the GBA-N370S mutation-associated PD transcriptomic and metabolic signature as well as selected protein abundance. Our analysis shows that GBA-PD-associated phenotypes are reproducible across organoid generation batches and time points. This proves that midbrain organoids are not only suitable for PD in vitro modeling but also represent robust and highly reproducible cellular models. © 2025 The Authors.

Authors Zuccoli E, Al Sawaf H, Tuzza M, Nickels SL, Zagare A, Schwamborn JC
Journal iScience
Publication Date 2025 Oct 17;28(10):113541
PubMed 41050933
PubMed Central PMC12494858
DOI 10.1016/j.isci.2025.113541

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