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In the last few years, one of the labs in the DPUK Stem Cell network has been at the forefront of a groundbreaking approach in Parkinson’s and dementia research: human cell models of neurodegenerative disease. Their pioneering work is deepening our understanding of what goes wrong in some types of brain cells, and it is fundamental to the screening of new drugs to combat degenerative processes.

Scientists working in the iPSC culture suite at the University of Oxford. This technology is available to the DPUK Stem Cells Network institutions. © Anna Lukala
Scientists working in the iPSC culture suite at the Oxford site in the DPUK Stem Cell network

Vital evidence base: human cell models of Parkinson’s disease

The human cell models in the Oxford lab are an important element in a whole range of complementary techniques in neurodegenerative research today. In addition to animal models and post mortem tissue studies, induced pluripotent stem cells (iPSCs) – a type of stem cell derived from adults – offer an improved human-centred angle on the diseases. Comparing the data from these different types of studies improves the robustness of insights we have in Parkinson’s and other diseases which lead to dementia. An example of this is this recent study which confirmed the role of the LRRK2 gene mutation in some forms of Parkinson’s. This is an example of the incremental work building up the understanding which allows precision drug screening and development work to take place.

In the last five years our ability to study human cell models of Parkinsons’ disease has come on leaps and bounds. The field is maturing, greatly deepening our understanding of why brain cells degenerate and die. Our work with human cell models is allowing us to undertake drug screening with partners with promising new targets.
- Professor Richard Wade-Martins, University of Oxford

Cohorts and stem cell research

These human cell models of neurodegenerative disease are possible thanks to samples from cohort study volunteers. In the case of the Parkinson’s research in Oxford, it is specifically thanks to skin biopsies from 100 members of the Oxford Parkinson’s Disease Centre (OPDC) Discovery cohort. This cohort (funded by Parkinson’s UK and now part of the DPUK group of cohorts) was started in 2010 and now has some 1600 members – some of whom are healthy volunteers, some with Parkinson’s and some at risk of Parkinson’s. The researchers developed and carried out complex techniques to convert fibroblasts – a type of human skin cell – first into stem cells and then into different types of brain cells, allowing study of the disease in living cells outside the human body. This is a more mature approach in neurodegenerative research. It's thanks to the cohort and highly advanced technologies that the researchers have been able to better understand which processes go wrong in some neurons, and why they die. 

Human cell models support drug screening for Parkinson’s

The human models offer improved understanding of the various degenerative processes that occur when Parkinson’s takes hold – a stage that is vital for the drug development done in industry. Researchers in the Oxford lab have been working with partners in industry (AstraZeneca) to test new drugs from its library of compounds. They have now completed the screening with four new potential drug targets to take forward to the next phase of testing.

There will not be a 'one size fits all' drug treatment for Parkinson’s or Alzheimer’s disease because there is not one single degenerative process that takes place in the cells. Cohorts like the OPDC cohort have allowed scientists to conduct studies which divide patients into groups, offering insights into which drug therapies will work for which patients.

More information

DPUK equipped labs in the UK Stem Cell network with industry standard machines to support collaborations and drug development with industry.