Can we replace lost brain cells for Parkinson’s patients?

As our health system becomes more efficient, life expectancy increases substantially. However, this means age-related diseases are becoming more prevalent, including Parkinson’s disease (PD), which is becoming a growing concern. Most cases arise from a complex combination of genetic, lifestyle, and environmental factors. Together, these factors trigger the harmful process at the heart of the disease: the gradual death of vital brain cells that produce dopamine.

Deep within our brain, the cells responsible for producing this chemical are called dopaminergic neurons. When these cells are lost, it does not just affect one spot; it disrupts the connections to other brain areas, much like a section of track disappearing from a busy railway line, preventing the train from completing its journey. Because dopamine is essential for movement, this disruption has visible effects. Consequently, Parkinson’s disease causes problems with movement, such as slowness or tremor, but it can also cause non-motor symptoms, including changes in mood and sleep.

Because Parkinson’s involves the loss of a specific cell population, researchers identified cell replacement as a potential strategy for a cure. Early attempts, such as those by the TransEuro consortium, faced ethical dilemmas, limited availability, and inconsistent results. Consequently, research shifted toward human pluripotent stem cells, immature ‘master cells’ that can be grown in the lab and have the ability to turn into any cell type in the body. Specifically, human embryonic stem cells (hESCs). While these are initially derived from early-stage embryos, they can be multiplied indefinitely in the laboratory, meaning there is no need for a fresh supply of embryos for every treatment.

Advances in the last two decades have enabled scientists to efficiently use these cells to generate the specific neurons lost in Parkinson’s. This has sparked a global race to provide a reliable source of cells that could offer long-term benefits, potentially slowing or reversing symptoms, reducing reliance on medication, and preventing the fluctuations that occur as drugs wear off.

Why is the study important?

This study is important to see if the positive results seen in animal studies can also be achieved in humans. Previously, researchers found that these cells successfully repaired tissue and improved movement in animal models using rats. Now, the plan is to put into patients, which could actually fix the damaged parts of the brain affected by Parkinson’s.

Additionally, they needed to ensure that the approach is safe and will not cause unwanted effects, such as tumours. A major fear with stem cell therapy is that the cells might grow out of control. To prevent this, the study used a high-standard ‘cell bank’ system to create a specific product (A9-DPC). This process involves treating immature stem cells so they become mature dopamine-producing cells that can no longer divide. This step is crucial because it minimizes the possibility of tumour formation, ensuring that no immature cells remain in the final preparation injected into patients.

The procedures were approved by the Ministry of Food and Drug Safety (MFDS) in Korea under Good Manufacturing Practice (GMP). This is a set of strict international safety rules ensuring that every medical product is created with the highest quality and is identical every single time.

What did the authors do and how did they do it?

After the researchers obtained specialized products, they then surgically implanted these cells into the specific brain regions of 12 volunteers who had been living with the disease for at least five years.

To determine the optimal treatment, participants were divided into two groups: one received a low number of cells and the other a high number. Following the surgery, the team used advanced brain imaging and physical exams to monitor the patients. Their goal was to confirm that this cell transplant was as safe and effective in people as it was in animal models.

To measure the real success of the transplant, patients underwent tests in an ‘off-medication state.’ This meant they stopped taking their regular Parkinson’s medication 12 hours before each evaluation, allowing doctors to see how well the new cells were working on their own. These assessments happened six times over the course of the year.

What are the results?

The study showed a positive outcome. The physical exams revealed that patients in both low and high-dose groups experienced better motor control and reduced symptoms when off their medication. These clinical results were supported by brain imaging, which showed evidence that the new cells were maturing and restoring connections in the areas where connections with dopamine neurones are lost. However, definitively confirming these physical connections will require long-term follow-up studies.

Regarding safety, patients had to take medication to prevent their bodies from rejecting the new cells, similar to the drugs patients take after a kidney or heart transplant. This medication caused some side effects. Nevertheless, these side effects were effectively treated. Additionally, one surgical side effect was reported: a small brain bleed in one participant, which fortunately caused no symptoms.

What do the findings mean going forward for people with the disease?

This study presents important findings for PD patients; however, there are limitations that need to be addressed before the treatment is considered fully effective. A primary limitation is the length of the trial, 12 months. Since repairing the brain is a slow process, researchers need to follow patients for a longer period to ensure the cells survive and provide a long-term effect. Additionally, the small number of participants and the single-centre setting make it difficult to fully assess rare side effects.

One of the most common complications historically seen with these types of therapies is the development of involuntary, uncontrolled movements. Fortunately, no such side effects were observed in this study. The results of this trial align with encouraging data from a very similar study in the United States and Canada, where the intervention was well-tolerated with a complete absence of GIDs over 18 months, making it promising for later-phase trials. GIDs (graft-induced dyskinesias) are involuntary movements occurring after transplantation.

Similarly, a study at Kyoto University Hospital using a slightly different preparation of cells also reported no GIDs or adverse effects 24 months after transplantation.

In contrast, earlier trials by the TransEuro consortium were unable to avoid these complications. However, the overall message remains positive: these therapies offer a solution that targets the core of the problem by providing a biological repair. As research expands globally, the critical remaining question is whether this treatment gives sufficient, long-lasting benefit to justify the costs and risks.

This study can be found at
www.cell.com/cell/fulltext/S0092-8674(25)01041-4

Lead Authors
Jin Woo Chang

Publication details including date of publication
Cell Volume 188, Issue 25p7036-7048.e11December 11, 2025 DOI: 10.1016/j.cell.2025.09.010