A major obstacle for Parkinson’s research has long been a lack of adequate methods to study the condition in human models. This is largely down to the inaccessibility of live dopamine neurons from vulnerable areas of the brain. The discovery of iPSCs in 2006 was heralded as the breakthrough of the decade, revolutionising the field. iPSCs enable non-invasive study in the laboratory of the same human neurons that are lost in Parkinson’s. However, while they are the best human model available, one limitation of current approaches is that dopamine neurons do not act alone in the brain. They interact with many other cell types and may heavily rely on these other cell types to combat stress and survive. According to Senior Research Fellow Dr Charmaine Lang: "The formation of more sophisticated iPSC models, where multiple brain cell types interact, just as they would in the human brain, is necessary for the drug discovery process."
Dr Lang has become the first recipient of a new jointly funded Senior Research Fellowship from Parkinson’s UK and Rosetrees Trust. The award will allow her to develop complex iPSC models to study the interaction of dopamine neurons with astrocytes, an integral support cell in the brain, and identify whether a lack of support from neighbouring astrocytes is contributing to dopamine neuron loss in Parkinson’s. She will use these models to screen repurposed compounds and identify which drugs reverse defects identified in Parkinson’s patient dopamine neurons. She will also use advanced microfluidic devices to grow iPSC dopamine neurons and astrocytes in specialised chambers, with and without physical interaction of these two cells, to gain further understanding on dopamine neuron and astrocyte communication and support in Parkinson’s.
Dr Lang said: "Many candidate therapeutic drugs fail on transition from bench to clinic, I believe in part, due to a lack of complex 'in a dish' models that more accurately represent the intricate interactions of live cells in the human brain. Improving human iPSC models is vital if we are to identify quality drugs that will successfully get through the clinical trials process and to people with Parkinson’s. The drug libraries which will be screened in this Fellowship are composed of compounds that have been thoroughly characterised, making them attractive candidates for downstream therapeutic approval in clinical trials. Additionally, all the data generated, will be disseminated throughout the scientific community and the information shared with people with Parkinson’s.
"I hope this work will hold significant long-term value for the wider research community and will generate much needed data surrounding the mechanistic understanding of dopamine neuron and astrocyte communication and support in Parkinson’s."
The award also allows Dr Lang to commence her first independent post within DPAG and the Kavli Institute for Nanoscience Discovery. As a Kavli team leader, she will build her own research group within the Wade-Martins laboratory.
Dr Lang said: “I am so grateful to both Parkinson’s UK and Rosetrees Trust for supporting early career researchers and for selecting me to be the recipient of this Fellowship. I am excited to use this opportunity to begin my independent journey, build my team and to expand on the techniques and expertise I have developed thus far. I am very lucky to have received a wealth of support and guidance from funders, colleagues within DPAG and the Kavli Institute and the patients within the Oxford branch of the Parkinson’s UK network. I look forward to the journey ahead and to giving back to the Parkinson’s patient community.”