Lay summary by Grace Denton, reviewed by Dr Scott Allen & a Parkinson’s Disease Lay Panel
Background
Parkinson’s disease (PD) is a condition where brain cells that produce dopamine, called dopamine neurones, don’t function properly. Dopamine is essential for controlling movement, therefore, break down of dopamine-producing cells in PD patients leads to problems with movement, including involuntary shakes. Scientists are investigating ways to replace these damaged cells to treat PD. This clinical trial tests whether transplanting dopamine-producing brain cells into the brain is an effective treatment for involuntary movement in PD patients such as shakes. The objective of the study was to determine whether stem cell treatment is safe to use in humans. The study used stem cells, a type of cell found in human embryos that can turn into specialised cells adapted to carry out a desired function, in this case, dopamine-producing brain cells.
Why is the study important?
Most available therapies lose effectiveness over time due to the lack of dopamine-producing brain cells present in people with PD. Therefore, replacing brain cell activity could offer longer-lasting results. Previous studies using stem cells have demonstrated promise, however several improvements were identified, such as finding a suitable source of dopamine-producing brain cells that passes quality control assessments and doesn’t contain any other unwanted cell types.
Other studies using models of PD allowed the development of a treatment called bemdaneprocel. Bemdaneprocel is a group of stem cells that are transplanted into the human brain to replace destroyed brain cells. This study, the first conducted in humans, assessed the safety of bemdaneprocel to treat impaired movement. In addition to documenting any side effects, the authors assessed whether the transplanted cells survived one year after implantation and how the treatment affected patients’ quality of life and movement.
What did the authors do and how did they do it?
The authors conducted a first-in-human trial to test the safety of bemdaneprocel. People with PD were treated with bemdaneprocel via surgical injections in different parts of the brain, then placed on immunosuppressants (drugs that lower the activity of the immune system) to prevent transplant rejection. People who had mobility issues or other brain-related conditions not caused by PD were excluded from this trial. The study had two groups: a low-dose group and a high-dose group. The high dose group were given a high dose of bemdaneprocel, which was three times larger than low dose. The goal of the high dose was to fully restore the number of dopamine-producing brain cells to normal levels while the low dose was designed to increase dopamine-producing brain cell numbers above their original levels, but not necessarily back to normal. This would help show whether the treatment is having a positive effect at all on involuntary movement in patients.
The authors conducted assessments of the patients 1 year after transplantation. A wide range of tests were carried out to determine if the new cells survived along with how well the medication worked by recording the periods of time where the patient has no involuntary movements or untroublesome movements compared to when they do. They also recorded how much other PD medication each person needed. Participants in the trial were also asked to complete questionnaires to rate their own quality of life following treatment. These results were analysed and processed to determine not only the safety of using bemdaneprocel but support further clinical trials of bemdaneprocel to determine its effectiveness to treat involuntary movement in PD.
What are the results?
Bemdaneprocel was deemed a safe and well-tolerated treatment for PD. Aside from one patient who experienced a mild seizure shortly after surgery, there were no serious side effects linked to the treatment. 18 months after treatment was started, there were 78 reports of side effects, however, none were linked to the bemdaneprocel treatment or the clinical trial. The transplantation method was also determined a success, with all transplanted cells injected successfully in the intended area of the person’s brain. Importantly, the transplanted brain cells were still alive after 18 months and therefore 6 months after patients stopped taking immunosuppressants.
This means that the transplanted cells were not rejected by the person’s body. While the main purpose of this study was to determine the safety of bemdaneprocel, other secondary results from numerous additional tests were promising. People with PD displayed fewer involuntary movements, even without the benefit of other PD medication. While these results require further investigation, these early findings suggest that bemdaneprocel could help improve movement in PD patients; the drug was well tolerated and showed potential as a new way to treat the condition.
What do the findings mean going forward for people with the disease?
The authors’ findings support moving forward with more clinical trials of bemdaneprocel. The results show that it is safe to use in humans with few side effects, but more testing is needed to understand how well it works in improving movement and reducing involuntary movements past the 18 months assessed in this clinical trial. Overall, the findings support the idea of using stem cells to replace lost dopamine-producing brain cells in people with PD to treat involuntary movement.
This study can be found at
Phase I trial of hES cell-derived dopaminergic neurons for Parkinson’s disease | Nature
Lead Authors
V. Tabar, C. Henchcliffe
Publication details including date of publication
Nature volume 641, pages 978–983. 16 April 2025