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Ludwig studies could help improve experimental stem cell therapies for Parkinson's disease
In two studies published in Cell Stem Cell, Ludwig Cancer Research scientists at Karolinska Institutet working with colleagues at Lund University present results that could significantly improve experimental stem cell-based therapies for Parkinson’s disease that are now approaching evaluation in clinical trials.
Parkinson’s is caused by the degeneration of the dopamine-producing cells in the brain, and researchers have been developing ways to use stem cells to generate such neural tissue for transplantation. The first paper, led by Ludwig Stockholm Director Thomas Perlmann and including Rickard Sandberg, a member of the same Branch, addresses the identity of cells that give rise to dopaminergic neurons. Applying single-cell RNA sequencing technology developed in Sandberg’s lab, the researchers profiled all the genes expressed in individual neuronal progenitors to pinpoint the origins of dopamine-producing cells in the mouse embryonic brain.
“We found, completely to our surprise, that during their early development, dopamine cells are very closely related to a type of cell that forms close to the area in which dopamine cells are normally formed,” says Perlmann. “The closely related cell type develops into what are called STN cells, which…don’t degenerate during Parkinson’s disease.” This revealed new markers that allowed researchers to distinguish between the two.
The second paper, in which Perlmann is a co-author, examined whether the information obtained in the first could be used to improve experimental stem cell therapies for Parkinson’s. The authors describe how they applied RNA sequencing to analyze global gene expression in more than 30 batches of neural grafts prepared from human embryonic stem cells. They found that the molecular markers currently used to capture progenitors of dopaminergic neurons generate subpar grafts because they capture neurons that make STN cells as well.
The researchers then applied the markers identified in the first study, and showed that this generates a far superior graft of dopaminergic neurons. Their method meets the standards of Good Manufacturing Practices required by regulatory authorities, and is ready for immediate use in clinical trials evaluating cell therapy for Parkinson’s disease.