Parkinson’s is characterised by the progressive loss of dopamine nerve cells (neurons) in an area of the brain associated with movement. Therefore, researchers have been investigating whether cell transplantations have potential to replace the neurons lost, to slow or reverse progression of the condition.
What was the study?
Launched in 2010, the TransEuro study was led by Professor Roger Barker at the University of Cambridge (UK) to evaluate whether cell transplantation therapy could slow the progression of Parkinson’s. The researchers modified fetal stem cells – cells able to develop into many different brain cell types – to create new dopamine neurons. The neurons were then surgically injected into the putamen, a part of the brain heavily affected by Parkinson’s. The purpose of the trial was to observe whether this treatment had a meaningful impact on Parkinson’s motor symptoms for those in early stages of the condition and whether it could restore near-normal levels of dopamine neurons in people with Parkinson’s.
Between 2015 and 2018, eleven people with Parkinson’s received cell transplantations, eight participants in Cambridge, UK and three in Lund, Sweden. Participants were required to take immunosuppressive therapy – medicine that prevents the body from attacking transplanted cells by suppressing the body’s defense systems – for 12 months after the operation.
Cure Parkinson’s funded a three-year follow-up study monitoring the participants, which also involved following a larger control group of 16 people with Parkinson’s. Participants took motor and cognitive assessments every six months for three years to establish a point of comparison in progression between those with a transplant and those without.
What were the results?
The results from the trial indicated that three years after transplantation there was no significant difference in motor symptoms between participants who received cell transplantations and people with Parkinson’s in the control group. Although there was evidence of a positive correlation between clinical effect and the number of surviving cells, the levels of dopamine neurons were not consistent between the participants, with only one participant showing near-to-normal levels.
Researchers suggested the variable results may relate to the difficulty of securing a consistent supply of fetal stem cells, which led to a number of surgeries needing to be rescheduled or cancelled throughout the trial. This also made it difficult for the researchers at the two centers to standardise the cells each participant received, as there was a large variation in the age of the cells used in each transplant. The supply issues of fetal cells meant that the methods used in the study are not feasible in the long-term for a wider population.
The trial also looked at whether the procedure used would avoid graft-induced dyskinesias (GIDs). Dyskinesia is an involuntary muscle movement sometimes seen in people with Parkinson’s following long-term use of the commonly used drug levodopa. However, in previous cell transplantation trials, researchers discovered that following surgery, several participants developed GIDs which are distinct from levodopa-induced dyskinesias. One of the goals of the TransEuro study was to determine whether the method used could reduce the number of GIDs; unfortunately, 27% of participants developed GIDs, indicating this approach did not lower the incidence rate.
Why is this important?
Although the trial did not meet its primary endpoint, insights from this study have helped inform the direction of future trials of cell transplantation for Parkinson’s. Firstly, the ongoing STEM-PD study – a trial being led by Prof Barker and Professor Gesine Paul-Visse at Lund University, Sweden – will use embryonic stem cells grown in the lab, overcoming many of the supply issues faced in TransEuro.
Secondly, TransEuro also highlighted the importance of cell survival post-transplantation to ensure the long-term survival of dopamine neurons. Moving forward, it will be important for trials to consider how best to support neuron survival, whether that be by using immunosuppressive medications or developing methods of using stem cells derived from the patients themselves, making the body more likely to accept them.
