The stem cell race to rewire the Parkinson’s brain

The last thing Andy remembers is the frame clamped to his skull and the quiet click of the surgical drill.

Doctors were injecting millions of lab-grown dopamine-producing brain cells – cells cultivated from embryonic stem cells – directly into his brain.

For Andy, living with Parkinson’s for over 15 years, it was both terrifying and hopeful.

“After being afraid to go to the dentist, I chose brain surgery. That tells you everything. It was terrifying – but I did it. Because if this helps – even a little – it will have been worth it,” he says.

“It wasn’t the surgery itself that scared me most,” he adds. “It was what came after – the relentless routine of 33 pills a day, each with its own timing and rules. In the end, my wife Nicola had to work with the clinical team to build a spreadsheet just to keep it all straight.”

“It’s strange,” Andy reflects. “I used to manage multi-million-pound IT development projects at British Telecom’s R&D Centre. Now, I find even basic household finances overwhelming. The little decisions pile up and become too much. That’s one of the more frustrating parts of living with Parkinson’s.”

Andy is one of just eight patients in a pioneering clinical trial. But he’s not alone.

Around the world, three teams – in Japan, the U.S., and Sweden – are testing whether stem cell–derived neurons can do what pills can’t: replace what Parkinson’s takes away.

The science is moving from lab to patient, but the outcome is still uncertain.

Why Parkinson’s has defied a cure

Parkinson’s disease affects more than ten million people worldwide. Parkinson’s doesn’t directly kill, but over time it causes severe disability and increases the risk of life-threatening complications.

“It’s frustrating,” says Andy, one of the first patients to receive a stem cell transplant. “After 200 years, we still don’t know what’s causing it. But I’ve learned to live with what I can’t control.”

The issue originates deep within the brain, where specialised nerve cells produce dopamine, a crucial chemical messenger responsible for smooth, coordinated muscle movements. As these cells die, patients lose motor function. Medication can help, but only temporarily. What patients lose, pills can’t replace.

For decades, scientists have dreamt of replacing the missing dopamine cells. Early attempts using transplantation of donated fetal brain tissue from abortions delivered promising clinical results, but were also unpredictable in outcome.

“Fetal tissue was excellent for proof-of-concept studies but is not a good strategy for developing a standardised treatment,” explains STEM-PD preclinical development lead, Agnete Kirkeby, Associate Professor at the Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), University of Copenhagen and Lund University, Sweden. “With stem cells, we have much better control of cell composition, product quality and consistency.”

The unpredictability was not just biological.

“The early trials with fetal tissue taught us that this approach can really work in patients, but also what can go wrong – the unpredictable survival of the cells, and side effects if the tissue is not implanted correctly. We have learnt from these trials to improve newer trials with lab-grown neurons.”

Despite growing optimism around stem cells, the first many years in the stem cell field have focused on showing that transplantation of lab-grown stem cells is safe.

“Now, more than 1200 patients world-wide have received treatments with lab-grown stem cells for many different kinds of diseases,” explains Kirkeby. “We’ve finally reached a point where we can start testing in larger trials whether the cells can actually help patients.”

It had taken years of frustration and false starts to get there.

“We always knew purity was the barrier,” Kirkeby reflects. “We spent over a decade just learning how to optimise the product to prevent overgrowth and to optimise efficacy. That groundwork made the next breakthroughs possible. This work has enabled us to go into patients with entirely lab-grown neurons for Parkinson’s disease.”

Kirkeby’s lab is continuously working to optimise the protocols for the dopamine cell production and has recently published a paper showing how the protocol can be tweaked for higher purity.

Dopamine nerve fibers seen through the microscope in the lab – the brain’s own signaling pathways.

The stem cell revolution

The idea of repairing the body with its own cells has long fascinated scientists.

In 2006, Japanese scientist Shinya Yamanaka discovered how to reprogram ordinary skin cells back into stem cells. These so-called induced master stem cells that can become any type of body cell, or iPS cells, have the power to become any cell type in the body. The breakthrough earned Yamanaka a Nobel Prize and transformed medical research.

Another type of stem cell – embryonic stem cells – had been studied since the 1990s. These cells, taken from early-stage embryos, also have the ability to develop into any cell type.

Scientists can start either with embryonic stem cells (derived from early embryos) or iPS cells (reprogrammed adult cells like skin cells). Although they originate differently, both types can become specialised neurons suitable for transplantation.

“The immediate difference is that the Japanese study uses iPS cells, and we and the U.S. study use embryonic stem cells. Also, the Japanese study needs to manufacture a new batch of cells for each individual patient, whereas the US and Swedish studies are using frozen cells which have been manufactured in large batches for many patients” says Agnete Kirkeby. “But the end product looks very similar, and in all three trials, we are aiming to transform the stem cells into the type of dopamine-producing neurons that die off in Parkinson’s disease.”

Three paths through the brain

As stem cell technology moved from laboratory success to patient trials, three research groups emerged at the forefront: one in Japan, one in the United States, and one in Sweden, where Agnete Kirkeby has the role of leading the preclinical development.

All three share the same goal: to restore dopamine production in the brains of people with Parkinson’s disease.

Beyond the cells themselves, the teams have fine-tuned many steps in how the cells are grown, prepared for transplantation, delivered surgically, and how immune suppression is managed afterward.

“Since 2014, we have met every year with the Kyoto and the U.S. groups as part of a network called G-Force,” says Agnete Kirkeby. “We decided early on to share knowledge – how we design the trials, select patients, calculate doses, and measure clinical outcomes. We knew that if any of us made a mistake, it would affect the whole field.”

She still remembers the day the first patient received a transplant. “It was emotional,” she says. “We’d worked over a decade for that moment. Watching it finally happen felt surreal.”

While some might see this as a race, the researchers themselves view it differently.

“We actually need comparison of the clinical efficacy between several products,” Kirkeby notes.

“I believe there will be space for several products on the market.”

The first patient

In 2023, the first patient in Europe – the Swedish-UK STEM-PD trial – received a transplant of dopamine-producing neurons at Skåne University Hospital in Sweden. Andy, the patient introduced at the start of this story, is the last of the eight participants.

The STEM-PD trial, led by teams from Sweden, and the United Kingdom, has transplanted eight patients with embryonic stem cell–derived dopamine neurons to assess safety and tolerability.

For Andy, deciding to join the trial was both frightening and liberating.

Before surgery, he had lived under a strict Parkinson’s medication routine.

“My Parkinson’s drugs are about 11 tablets a day,” he says.

After surgery, the number of pills soared.

“It jumped up to 33 tablets a day – my normal Parkinson’s drugs, plus immunosuppressants and steroids to help the transplanted cells survive,” Andy explains.

“I had to develop quite a complex spreadsheet, even for a spreadsheet nerd, to cope with it: some tablets before food, some with food, some after food.”

Yet surgery also brought a sense of hope and purpose.

“I feel like I’m nurturing these immature cells in my head,” Andy says of the transplanted cells. “I know they’re fragile. I don’t want to do anything that might hurt them. I’ve got this tiny Harry Potter-like scar from the surgery,” Andy laughs. “I’m quite proud of it. Sometimes I run my fingers over the scar when I’m nervous. It reminds me I took a risk—maybe the biggest one of my life.”

Andy lives with what he calls fragile cells. “Sometimes I touch the scar – it reminds me I took a chance.”

First signs of hope

This month, two additional international trials reported their first safety trial results.

In the United States, BlueRock Therapeutics transplanted embryonic stem cell–derived dopamine-producing brain cells into 12 patients.

In Japan, researchers at Kyoto University led by Jun Takahashi treated seven patients using iPS cells reprogrammed from adult skin cells.

The outcomes are remarkably consistent.

Encouragingly, none of the studies report serious adverse effects—no tumours, severe involuntary movements, or immune rejection. Yet, these findings are preliminary; long-term safety and effectiveness remain uncertain and require further monitoring.

While the trials are designed to test safety, researchers also see early signs that the transplanted cells are beginning to function.

Hoping everything inside is quietly developing

In both the U.S. and Japanese trials, brain scans show that the cells survive and start producing dopamine.

In the U.S. trial, the high-dose group showed an improvement in motor scores by an average of 23 points on the standard Parkinson’s scale, corresponding to a 50% reduction in symptoms.

In the Kyoto trial, PET scans show a 45% increase in dopamine uptake.

Four of six evaluated patients improved their motor scores by an average of 9.5 points.

The STEM-PD trial is still ongoing, and while Andy was only transplanted 7 month ago, he already feels a complex mixture of hope and patience.

“It’s a strange kind of waiting,” he says. “You want to believe something’s changing, even if you can’t feel it yet.”

Andy knows the transplanted cells may take up to two or three years to fully integrate and begin restoring lost function. “It feels like a long, invisible process of nurturing,” he says, “where you’re hoping everything inside is quietly developing the way it should.”

“We’ve seen evidence from the first small trials that the stem-cell-derived neurons are safe, can survive and produce dopamine in the human brain” says Kirkeby. “Now, we’re expecting to see 3 larger clinical trials to be initiated during 2025 and 2026 with the aim of assessing the clinical efficacy of the stem cell products.”

How much is enough for success

The early trials are designed to prioritise safety above all else. That means starting with low doses of cells. But early patient data hint that dosage may matter more than expected.

“It only works if the cells survive,” says Agnete Kirkeby. “When scans show more dopamine after higher doses, that’s the signal we’re looking for: the cells are working.”

In the U.S. study, the high-dose group shows a larger motor improvement than the low-dose group.

“We saw a stronger dopamine signal and better clinical effects in patients who got the higher dose,” says Kirkeby.

Finding the right dose and the right patient population remains one of the next great challenges.

Should future studies transplant cells earlier in the disease course, when patients still have some healthy neurons to support the graft?

Or should they focus on patients with more advanced disease, who have the most to gain but may be harder to treat?

“Some patients are still doing fine on their medication,” says Kirkeby. “The real impact might not show for five or ten years – that’s the goal.”

From science to business

For years, stem cell researchers have collaborated closely as academics. They shared protocols, compared patient selection criteria, and aligned on how to measure clinical outcomes.

“We decided early on to share knowledge,” says Agnete Kirkeby. “We knew that if any of us made a mistake, it would affect the whole field.”

It has raised a lot of discussion, when the U.S. Food and Drug Administration (FDA) made a surprise decision early in 2025: to allow BlueRock Therapeutics to skip Phase 2 and proceed directly to a large Phase 3 clinical trial.

“We were all shocked,” says Kirkeby. “The FDA fast-tracked a trial, and it surprised everyone,” says Kirkeby. “But they did so because the safety data was solid.”

The decision instantly changed the dynamic. While trials have until now progressed cautiously with small safety studies, the U.S. team is now racing to become the first approved product.

As all three teams are now partnering with large pharma companies to conduct the next clinical trials, we will be looking into a race towards market authorisation in the coming years.

“I hope to see more than one product make it to the market,” Kirkeby says. “This would help keep prices down and make the therapies available to more patients.”

Agnete Kirkeby together with Andy.

A field just beginning

After decades of hard work, the first stem cell transplants for Parkinson’s are beginning to deliver long-awaited results.

Yet no one in the field believes the work is done. The question now shifts from safety to scale.

How can the process be optimised? How many patients can ultimately benefit?

Researchers know the path to affordable access may depend on more than just scientific success.

“The more players involved, the better chance we have of keeping this affordable and available to patients everywhere,” says Kirkeby.

The spirit of global cooperation remains for now.

“If one of us fails, we all lose,” says Kirkeby. “We’ve shared protocols, doses, patient selection guidelines. Because if anyone makes a clinical mistake, it could damage the field for everyone.”

Andy remains cautiously optimistic.

“I’m just one dot on the chart,” Andy says. “Individually, I may be insignificant – but together we’re shaping the future. Ask me again in two or three years. Right now, I feel like I’ve been handed this tiny seed, and my job is just to help it grow. I know it takes time.”

The starting gun has fired.

What happens next will determine whether stem cell therapy truly becomes the breakthrough that people with Parkinson’s have waited for — and for Andy, whether a quiet revolution inside his brain will one day change everything.