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ePoster
HUMAN MIDBRAIN ORGANOIDS TO STUDY THE ROLE OF C19ORF12 IN PARKINSON’S DISEASE
Carolina Pivaand 3 co-authors
Erasmus MC
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS03-08AM-083
Presentation
Date TBA
Board: PS03-08AM-083
Event Information
Poster Board
PS03-08AM-083
Poster
View posterAbstract
Mitochondrial membrane protein–associated neurodegeneration (MPAN) is a subtype of Neurodegeneration with Brain Iron Accumulation (NBIA) caused by pathogenic variants in C19orf12. Brain autopsies of C19orf12 mutation carriers revealed presence of Lewy bodies, a pathological hallmark of Parkinson’s disease (PD), suggesting a link between MPAN and PD. Disease-causing variants impair C19orf12 localization and activity, leading to mitochondrial dysfunction, altered lipid metabolism, and defective autophagy/mitophagy. However, the physiological role of C19orf12 and its contribution to neurodegeneration remain unclear.
To elucidate C19orf12 function and its relationship with PD, this study aims to generate human iPSC–derived in vitro models (2D neuronal/glial cultures and 3D human midbrain organoids (hMOs)) using established protocols. Functional analyses will assess neuronal function and degeneration via immunohistochemical analyses, mitochondrial oxygen consumption assays, and assessments of neuronal activity and survival. We will also investigate α-synuclein aggregation and Lewy body–like pathology as well as iron accumulation. Unbiased transcriptomic and proteomic approaches will be used to gain more insight into disease mechanisms. Via a FACS-based CRISPR-Cas9 editing approach we have successfully generated C19orf12 KO lines (heterozygous, compound heterozygous) in two independent healthy control smNPC lines that have been validated by genotyping and Western blot analysis. Preliminary immunohistochemical analysis of wild type 2D neuronal smNPC-derived cultures demonstrates neuronal and glial C19orf12 expression.
This work will provide insight into C19orf12 physiological function and the mechanisms linking its pathogenic variants in C19orf12 to NBIA and PD.
To elucidate C19orf12 function and its relationship with PD, this study aims to generate human iPSC–derived in vitro models (2D neuronal/glial cultures and 3D human midbrain organoids (hMOs)) using established protocols. Functional analyses will assess neuronal function and degeneration via immunohistochemical analyses, mitochondrial oxygen consumption assays, and assessments of neuronal activity and survival. We will also investigate α-synuclein aggregation and Lewy body–like pathology as well as iron accumulation. Unbiased transcriptomic and proteomic approaches will be used to gain more insight into disease mechanisms. Via a FACS-based CRISPR-Cas9 editing approach we have successfully generated C19orf12 KO lines (heterozygous, compound heterozygous) in two independent healthy control smNPC lines that have been validated by genotyping and Western blot analysis. Preliminary immunohistochemical analysis of wild type 2D neuronal smNPC-derived cultures demonstrates neuronal and glial C19orf12 expression.
This work will provide insight into C19orf12 physiological function and the mechanisms linking its pathogenic variants in C19orf12 to NBIA and PD.
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