Although Parkinson’s disease is not a rare condition and many researchers are working on it around the world, its causes remain mysterious: we still do not know why people get this progressive neurological disease in the majority of cases and we currently have no cure. What we do know is that individuals with Parkinson’s do not produce enough dopamine and this is because some of the nerve cells, or neurons, that make this chemical in their brains have died. To move towards an effective cure, we need to know how and why these neurons die. That requires focussed study of these human disease-relevant dopaminergic and cortical neurons, but to generate these neurons has proved challenging. In 2014 the Evelyn Trust funded a one-year project that promised to tackle this key issue.

Led by Professor Roger Barker, Professor of Clinical Neuroscience at the John van Geest Centre for Brain Repair, University of Cambridge, a talented research team has used skin biopsies taken from patients with Parkinson’s disease to grow up skin cells which they can then turn into neurons. Critically, however, the team also manipulated the procedure in order to turn these skin cells into more mature neurons – as it is clear that Parkinson’s disease affects elderly people who have very mature neurons. The main breakthrough is that they can now generate nerve cells that show the same functional characteristics as the mature nerve cells of the adult brain, making them better models for the study of diseases such as Parkinson’s. This is an important advance on previous techniques used to reprogramme such cells, as the nerve cells so generated looked and functioned more like the neurons found in embryos, rather than mature adult cells. The availability of these mature brain cells will now mean that they can do much more effective disease modelling in the culture dish which will shed light on the causes of Parkinson’s disease, and will also prove invaluable in the testing of new therapies.

“The technique we are using is called ‘transdifferentiation’ - it’s genuinely innovative and it has enormous potential. Creating disease-specific neurons from skin cells will help us to gain a clearer understanding of what’s causing the degeneration of an individual’s dopaminergic neurons inside their brain, leading ultimately to personalised treatments,” explains Dr Fahad Ali from the team at the Barker Lab.

As part of the project, skin biopsies were also taken from patients with Gaucher disease, a serious metabolic disorder caused by mutations in the glucocerebrosidase (GBA) gene that sometimes occurs with Parkinson’s. Professor Barker’s team is now using the reprogrammed cells to better understand the link between Parkinson’s and Gaucher disease.

The research at the Barker Lab was undertaken by Dr Fahad Ali and the team collaborated with Dr Anna Philpott from the Department of Oncology and Dr Malin Parmar,a researcher in neurobiology from Sweden’s Lund University.