Human Trials of Stem Cell-Derived Dopamine Neurons Offer Hope for Parkinson’s

Key Takeaways:

Stem cell-derived dopamine neurons were safely transplanted into Parkinson’s patients in two clinical trials.
Some patients showed improved motor symptoms, especially in the high-dose groups, with no tumor formation or serious side effects.
No graft-induced dyskinesias were reported, marking a major improvement over earlier fetal tissue transplants.

Transplanted Dopamine Neurons Credit: Nature

Two recent clinical trials have provided early evidence that lab-grown dopamine-producing neurons can be safely transplanted into the brains of Parkinson’s patients, offering a potential regenerative treatment. Published in Nature, the studies mark a major milestone in stem-cell-based therapies, but experts caution that longer-term studies are needed to fully assess their benefits.

Why Scientists Are Exploring Cell Therapy for Parkinson’s

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra. This leads to hallmark motor symptoms such as bradykinesia, rigidity, tremor, and postural instability.

While medications like levodopa help in early stages, their efficacy wanes over time, often leading to side effects like dyskinesia. Researchers are now testing whether replacing lost dopamine neurons through cell transplantation could provide more durable symptom relief, or even alter disease progression.

Trial 1: Japan’s iPSC-Based Cell Therapy

Researchers at Kyoto University conducted a phase I/II clinical trial using dopaminergic progenitor cells derived from induced pluripotent stem cells (iPSCs). Seven patients aged 50 to 69 underwent bilateral striatal transplantation, with three receiving a low dose and four receiving a high dose.

Key Details:

Safety: Over 24 months, there were no serious adverse events or tumor formation. All grafts remained stable in size, and no inflammation was detected via PET or MRI imaging.
Motor Outcomes:
- In the medication-OFF state, 4 of 6 patients showed motor improvement. The average improvement was −9.5 points (−20.4%) on the MDS-UPDRS Part III.
- In the ON state, 5 of 6 patients improved, with an average decrease of −4.3 points (−35.7%).
- Hoehn–Yahr stage improved in 4 patients, with one patient improving by two stages.
Imaging Evidence: PET scans showed an average 44.7% increase in 18F-DOPA uptake in the putamen, confirming dopamine production. This increase was 63.5% in the high-dose group, indicating possible dose-dependent benefits.
Medication: Doses of anti-parkinsonian medications were largely maintained to isolate the graft’s effect, which may explain the observed increase in dyskinesia scores.
Adverse Events: Most side effects were mild. One case of dystonia and several tacrolimus-associated effects (e.g., liver enzyme elevations) were managed successfully.

Importantly, no graft-induced dyskinesias (GIDs) were reported—a concern in earlier fetal tissue transplant studies—likely due to purification methods that eliminated serotonergic neurons.

Trial 2: U.S. Study Using hES-Derived Dopaminergic Cells (Bemdaneprocel)

In the United States, researchers tested a new cell therapy called bemdaneprocel, derived from human embryonic stem cells (hES cells).

Twelve participants received bilateral putaminal grafts: five in a low-dose group (0.9 million cells/putamen) and seven in a high-dose group (2.7 million cells/putamen).

Key Results at 18 Months:

Safety: No cell-related serious adverse events occurred. One patient had a seizure (linked to surgery), and another experienced a GI bleed unrelated to the treatment. No tumor formation, hemorrhage, or GIDs were observed.
Motor Outcomes (MDS-UPDRS Part III, OFF state):
- Low-dose group: average improvement of 8.6 points
- High-dose group: average improvement of 23.0 points, considered a clinically meaningful change
Functional Time Gains:
- High-dose group gained 2.7 additional hours per day of “good ON time” (without disabling dyskinesia)
Imaging Confirmation:
- PET scans demonstrated increased 18F-DOPA uptake in the putamen, supporting graft survival and dopamine synthesis.

Like the Japanese study, no serotonergic contaminants were found in the grafts, reducing the risk of dyskinesia. All patients received immunosuppressants for one year post-op, including tacrolimus and steroids.

What Experts Are Saying

“These two trials independently demonstrate that dopamine-producing stem cell grafts can survive and function in the human brain without causing serious side effects,” said Dr. Angela Park, a neurologist at Johns Hopkins. “It’s early, but the data are extremely encouraging for the future of cell-based therapies.”

Both studies noted the absence of GIDs, one of the most serious complications seen in earlier fetal transplant efforts, as a critical success point. Researchers attribute this improvement to advanced cell sorting techniques that eliminate serotonergic and other off-target cells.

The Road Ahead

Despite the positive results, these were open-label, non-randomized trials with small sample sizes. More definitive data will need to come from blinded, placebo-controlled, multi-center phase III trials.

Still, the consistent safety signals and observed motor improvements suggest that stem-cell therapy may soon become a foundational option for patients with advanced Parkinson’s.

Future directions include:

Optimizing cell dosage and delivery strategies
Identifying ideal patient profiles (e.g., age, disease stage)
Investigating autologous grafts using patient-specific iPSCs
Exploring combination therapies with rehabilitation or gene therapy

FAQs: Understanding Parkinson’s and the Stem Cell Trials

What is Parkinson’s disease?
A brain disorder caused by the loss of dopamine-producing neurons. It leads to tremors, stiffness, and slow movement.

What causes it?
Mostly unknown. Aging, genetics, and environmental factors may play a role.

How is it usually treated?
With drugs like levodopa that replace dopamine. These help symptoms but don’t stop the disease.

Why are new treatments needed?
Current drugs lose effect over time and can cause side effects like involuntary movements.

What is stem cell therapy?
A way to replace lost brain cells by transplanting lab-grown dopamine neurons into the brain.

What kind of stem cells were used?
The Japanese trial used induced pluripotent stem cells (iPSCs), which are adult cells reprogrammed to behave like embryonic stem cells. The U.S. trial used human embryonic stem cells, which are taken from early-stage embryos and grown into dopamine-producing neurons.

What is bemdaneprocel?
It’s an experimental stem cell therapy made from human embryonic stem cells, designed to replace lost dopamine neurons in Parkinson’s patients.

Where were the cells placed?
In the putamen, a brain area involved in movement control.

How do we know the cells worked?
Brain scans showed increased dopamine activity. Some patients moved better after treatment.

Were there side effects?
No major ones. Most were mild. No tumors or immune rejection.

What’s different from past cell therapies?
These cells were purified to avoid harmful types like serotonergic neurons, which in earlier trials caused graft-induced dyskinesias. This purification process may explain the improved safety profile.

Will this cure Parkinson’s?
No, but it may offer longer-lasting symptom relief.

What happens next?
Larger trials to test long-term safety and how well it works in more people.

How could this improve my quality of life?
If proven effective, it may reduce motor symptoms and medication dependence, improving movement, independence, and daily function.

Is this therapy available now?
Not yet. These are early trials. The treatment is still experimental and not approved for general use.

Will it be affordable or covered by insurance?
Unclear. These therapies are expensive and complex. Widespread access may take years and depend on trial outcomes, FDA approval, and health system support.

Are there other new treatments in development?
Yes. Researchers are testing:

Gene therapies that boost dopamine production
Anti-alpha-synuclein antibodies to slow progression
GLP-1 receptor agonists like exenatide for neuroprotection
Focused ultrasound and brain stimulation for symptom relief

Should I join a clinical trial?
Possibly, if you’re eligible and live near a trial site. Ask your neurologist about open studies and whether you qualify.

Bottom Line

These studies mark a turning point. For the first time, stem-cell-derived dopamine neurons have been shown to survive in the human brain, make dopamine, and lead to measurable motor improvements—without triggering serious side effects or graft-induced dyskinesias. That alone is a huge step.

But we’re not there yet. The trials were small, unblinded, and improvements varied. Some patients got better. Others didn’t. Placebo can’t be ruled out. So, can this approach scale? Will the benefits hold over 5 or 10 years? And will the grafts integrate deeply enough to restore complex brain function, or just patch it?

There’s also a practical hurdle: these treatments are technically demanding and expensive. Manufacturing cells, matching them to patients, and delivering them via brain surgery isn’t something every clinic can do. At least not yet.

Still, this is no longer theoretical. These trials suggest cell therapy for Parkinson’s is not only possible—it’s probably coming. If follow-up studies show real, lasting benefit, this could be the first regenerative therapy to change the course of a neurodegenerative disease.

The question isn’t just will it work—it’s how far can it go?

References

Sawamoto, N. et al. Phase I/II trial of iPS-cell-derived dopaminergic cells for Parkinson’s disease. Nature (2025). https://doi.org/10.1038/s41586-025-08700-0

Tabar, V. et al. Phase I trial of hES cell-derived dopaminergic neurons for Parkinson’s disease. Nature (2025). https://doi.org/10.1038/s41586-025-08845-y