Abstract

Midbrain Organoids for Parkinson’s Disease Modeling

Cláudia Saraiva, Post-Doctoral Researcher, University of Luxembourg

Parkinson’s disease (PD) is the second most prevalent disorder worldwide and its incidence is rising. Nevertheless, few advances in PD treatment have been observed. Therefore, understanding of PD associated mechanisms using novel complex and translatable models is timely. In our lab, we developed 3D cultures that resemble the human midbrain (midbrain organoids, MOs) through guided differentiation of induced pluripotent stem cells (iPSCs). The MOs are a complex system in terms of cellular composition and structural organization. Using PD patient-derived MOs we demonstrate that not only they resemble the midbrain organization but they also recapitulate key features of the PD pathology, such as dopaminergic neuron differentiation. Using this technology, we are currently investigating the role of the recently described Miro1 protein in dopaminergic differentiation in PD. Using high content imaging and western blotting we observed that a gain-of-function in Miro1 results in lower levels of dopaminergic neuros. Also Miro1-mutant MOs show a mitochondrial impairment when compared with healthy controls. Altogether, this work shows the importance of Miro1 in the pathology of Parkinson, and shed light into a possible novel and convergent pathway in PD.