New pluripotent stem cell line generated from a Parkinson’s disease patient is aimed at studying PD mechanisms and as a drug-screening platform

Denham group at DANDRITE and colleague researchers have developed a new stem cell line (DANi-011A) from a Parkinson’s disease (PD) patient carrying a LRRK2 p.G2019S mutation that is identified in inherited and sporadic cases of PD. The established cell line enables in vitro modelling of PD and the development of potential treatment strategies for neurodegenerative disorders.

LRRK2, DANi-011A, iPSC line generated by Sendai virus reprogramming. A) iPSCs stain positive for Alkaline phosphatase. B) Expression of pluripotent markers OCT4 and NANOG. C) DNA sequencing confirms the LRRK2 G2019S variant. D) Reprogrammed iPSCs no longer contain Sendai viruses. Credit: Denham group

The Denham group at DANDRITE use human embryonic stem cells and induced pluripotent stem cells to investigate neurodegenerative disorders such as PD. Mark Denham’s lab specialise in the generation and differentiation of neural cell types, thereby creating in vitro models for uncovering key molecular mechanisms in neurodegenerative diseases. In their latest study, the group have used fibroblasts of a clinically diagnosed 70-year old female PD patient to generate an induced pluripotent stem cell (iPSC) line with a LRRK2 p.G2019S variant. Denham lab used a non-integrating RNA virus (Sendai virus) to efficiently reprogram fibroblasts following the generation of human iPSCs expressing specific pluripotent markers.  The new stem cell line effectively formed embryoid bodies and neurospheres in which three different germ layers were identified by specific expression markers (ectoderm; PAX6/SOX2, mesoderm; BRACHYURY and endoderm, SOX17/FOXA2). The DANi-011A cell line can be used to study LRRK2 disease mechanisms as well as in a drug-screening platform.

Future studies using this line are aimed at understanding why a significant proportion of people with this pathological variant do not develop Parkinson’s disease. Specifically, the Denham lab is interested in identifying novel genetic variants that along with a LRRK2 variant contribute to the neurodegenerative process.

The publication can be read in full here.

Click here to learn more about the Denham group and their research within neural development, neurodegenerative disease and stem cells.