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Breakthrough Discovery Unravels Metabolic Mysteries in Sporadic Parkinson’s Disease Etiology

Featured Publication, Stem Cells, IDG, ISBM,

Sporadic Parkinson's Disease (sPD) is a progressive neurodegenerative disorder influenced by both genetic and environmental factors. While mitochondrial dysfunction contributes to this condition, its role across disease progression remains unclear. Using induced pluripotent stem cells (hiPSCs) of sPD patients it is shown that already neural precursor cells as well as young dopaminergic neurons show a reduced mitochondrial and thus metabolic activity.

In a landmark study, a team around Helmholtz Munich scientists Dr. Sebastian Schmidt and Prof. Wolfgang Wurst has unveiled critical insights into the metabolic intricacies of Sporadic Parkinson’s Disease (sPD). The etiology of this progressive and still incurable neurodegenerative disorder has long baffled scientists.

Using iPSC-derived neural cells and cutting-edge multi-omics approach, the team identified mitochondrial and metabolic alterations, including a bottleneck in the citric acid cycle's α-ketoglutarate dehydrogenase complex (OGDHC) activity, as key player in sPD progression. Furthermore, the study revealed that modulating the SHH signal transduction pathway could restore OGDHC activity and alleviate hypometabolism, offering a potential neuroprotective therapy during early sPD stages. A decade-long follow-up study with patients mirrored the cellular model findings, solidifying the link between hypometabolism, OGDHC activity, and sPD progression.

Published in Nature Communications, this research breakthrough paves the way for innovative therapeutic strategies and represents a significant leap in understanding and treating Sporadic Parkinson’s Disease.


Original publication

Schmidt et. al (2023): A reversible state of hypometabolism in a human cellular model of sporadic Parkinson’s disease. Nature communications. DOI: 10.1038/s41467-023-42862-7

About the scientists

Dr, Sebastian Schmidt, Postdoctoral Researcher at the Institute of Developmental Genetics and the Institute for Synthetic Biomedicine at Helmholtz Munich and at the Technical University of Munich (TUM)

Prof. Wolfgang Wurst, Director at the Institute of Developmental Genetics at Helmholtz Munich