Authors: Barbuti PA, Ohnmacht J, Santos BFR, Antony PM, Massart F, Cruciani G, Dording CM, Pavelka L, Casadei N, Kwon YJ, and Krüger R.
Scientific Reports, 2021.
Modeling Parkinson’s disease using patient-derived cells may facilitate the discovery of early-stage PD biomarkers
Parkinson’s disease (PD) is a progressive neurological condition characterized by the degeneration of A9 dopaminergic neurons and the abnormal formation of Lewy bodies composed of misfolded alpha-synuclein. Although the causes of PD are not fully understood, mutations in the SCNA gene that makes the protein alpha-synuclein are known to be associated with early-onset PD. In this study, scientists comparing patient-derived induced pluripotent stem cells (iPSCs) with gene-corrected clones describe for the first time the mutation-only effect of the p.A30P SNCA gene mutation on neuronal function and demonstrate reduced mitochondrial respiration, an energy deficit, transcriptional alterations in lipid metabolism, and vulnerability to rotenone.
To explore neural activity, scientists used Axion’s Maestro multielectrode array (MEA) platform. The results demonstrated that neurons carrying the A30P mutation exhibited reduced neuronal function with decreased mean firing rate, decreased number of synchronized bursts, and decreased percentage of bursts compared to the gene-corrected clones. Taken together with other findings, the authors conclude that these results support the use of isogenic patient-derived gene-corrected cell lines for disease modeling in PD and suggest the platform may facilitate the discovery of early-stage PD biomarkers and potential therapeutics in the future.
