Professor Roger Barker reconsiders the use of foetal cell transplants and explores the next generation of stem cell therapies for patients suffering with Parkinson’s disease. This research could allow cell-based therapies to become the norm in the treatment of brain diseases.
Professor Roger Barker
Department of Clinical Neurosciences / WT-MRC Stem Cell Institute
Approximately 130,000 new cases of Parkinson’s disease are diagnosed every year across Europe and the USA. The disorder is characterised by the degeneration of dopamine-producing neurons in the brain. Patients experience progressive motor problems with increasingly severe immobility as levels of dopamine, a neurotransmitter essential for normal movement, are depleted in the brain. Drugs such as L-DOPA aim to replace this lost dopamine and can have major benefits for the patients, but over time these treatments lose their efficacy and cause severe side-effects, which become increasingly debilitating.
To improve on standard drug treatments, the concept of transplanting new dopamine cells into the brains of patients with Parkinson’s disease was pioneered in a series of trials between 1987 and 2003 using fetal tissue. In theory, this therapy should have led to dramatic improvements by repairing the lost local network of dopamine cells. Unfortunately, these controversial early studies produced conflicting results; while some patients responded so well that other dopamine medication could be discontinued, others developed side-effects. As a result, cell transplantation for Parkinson’s disease was considered too variable to be of value and this approach ground to a halt.
Back in 2006, Professor Roger Barker launched a new initiative to re-evaluate all the data from the previous fetal cell transplant trials. This work systematically uncovered problems in trial design, patient selection, tissue preparation, and immunotherapy used post-grafting to prevent graft rejection, all of which had had contributed to the variable results – but crucially showed that the technique was worth taking back to the clinic if these parameters could be better controlled.
In 2010, he formed a new European collaboration, TRANSEURO, to undertake a new trial of fetal dopamine cell transplants in patients with Parkinson’s disease. Aiming to perform cell transplants in a dozen or so patients from the UK and Sweden, the trial will finish grafting in 2017 and will provide an initial report on their efficacy in 2020.
In tandem, Professor Barker and his team are working to develop the next generation of cell-based therapies derived from human embryonic stem cells and from induced pluripotent stem cells – a recent breakthrough where mature cells can be reprogrammed to a different cell type via a neutral stem cell-like state. These approaches would resolve the issues of cell availability and provenance that limit the use of fetal-derived dopamine-producing cells – and, if effective, would far surpass all other current therapies for Parkinson’s disease in the clinic.
He sees the TRANSEURO trial as setting the gold standard by which the new stem cell-based therapies can be assessed, “Although stem cell therapies are at an earlier stage than fetal cell transplantation, they have the potential to transform the treatment of Parkinson’s disease along with other chronic brain diseases and to benefit huge numbers of patients.”
Professor Barker and his colleagues look to a future where cell transplants for brain diseases become the norm rather than the preserve of experimental trials.
Barker RA et al. Lancet Neurol. 2013; 12(1):84-91
Barker RA et al. Nat Rev Neurol. 2015; 11(9):492-503
Kirkeby A et al. Cell Stem Cell. 2017; 20:135–148
This work is supported by the European Commission, MRC, NIHR Cambridge Biomedical Research Centre, Parkinson’s UK, Cure Parkinson’s Trust and the Rosetrees Trust.
