Landmark trials using stem cells to treat Parkinson’s disease in the USA and Japan mark a turning point for cell therapy in neurodegeneration. Similar approaches to Alzheimer’s disease and amyotrophic lateral sclerosis are also showing early signs of promise.
By Natalie Healey, 04 June 2025
During the height of New York City’s COVID-19 lockdown, a small group of people with Parkinson’s disease arrived at Memorial Sloan Kettering Cancer Center for an experimental neurosurgical procedure: the implantation of dopamine-producing neurons grown from human embryonic stem cells. Now, the researchers behind the trial have published results from that phase 1 study, showing that the transplanted cells survived, released dopamine and were well tolerated1. Some participants even experienced visible reductions in tremors.
The findings were encouraging enough for the US Food and Drug Administration to grant the program special status as a regenerative medicine advanced therapy and a fast-track designation, enabling the team to move directly into a phase 3 trial. It has taken over 20 years to get to this point, says stem cell biologist Lorenz Studer at Memorial Sloan Kettering Cancer Center, who co-led the project alongside colleague Viviane Tabar. “Results on both the safety side and what we can tell about the efficacy look quite promising. So we really couldn’t have hoped for much better at this stage.”
The trial, sponsored by BlueRock Therapeutics, a biotechnology firm based in Cambridge, Massachusetts, where Studer and Tabar are scientific co-founders, marks an important turning point in the pursuit of regenerative therapies for neurodegenerative disease — a field long hindered by the limits of conventional drugs. Stem-cell therapy offers the potential to replace or protect dying neurons and halt the progression of devastating neurological illnesses. But researchers bringing such therapies to the clinic face many complexities.
Progress in Parkinson’s disease
Studer and Tabar’s team is not the only group seeing success with stem-cell transplantation in Parkinson’s disease. In Japan, researchers completed a phase 1/2 trial, published in Nature2, this time using adult donor cells reverted to a pluripotent state (induced pluripotent cells) and then coaxed into becoming neural progenitor cells. Over the course of the 2-year study, the team observed no major safety issues in seven patients treated at Kyoto University Hospital, and some participants saw improvements in their symptoms of Parkinson’s disease. Other groups, including a team led by Malin Parmar in Lund, Sweden, are also preparing preliminary trial results for stem-cell therapy in Parkinson's disease. An international collaboration, coordinated through the GForce-PD consortium, is helping the field progress faster and more safely, says Tabar.
Among brain diseases, Parkinson’s disease is widely considered the ‘poster child’ for stem-cell therapy, explains Tabar. That is because it involves the loss of a single, well-characterized type of neuron. “If we can make this work, it opens the door to tackling much more complex conditions,” she adds. The team’s upcoming phase 3 trial will include 102 participants, with a primary endpoint looking at improvement in patients' movement symptoms over 78 weeks, and will include sham surgeries as a control.
Still, even in Parkinson’s disease, challenges remain, explains Clive Svendsen, a neuroscientist at Cedars-Sinai Medical Center, in Los Angeles, California. In the disease, the dopamine neurons lost are in the brainstem and project all the way to the striatum. Injecting stem cell therapies into the striatum therefore does not fully restore the neural loop. “If the dopamine neurons are not in the circuit correctly, or they're firing too much, you can have what's called runaway dyskinesias — abnormal movement induced by the transplant,” says Svendsen. However, Studer says there was no evidence of dyskinesias, or other serious side effects, in their trial at Memorial Sloan Kettering Cancer Center.
Rebuilding the brain
Although Parkinson’s disease currently dominates the spotlight, stem-cell therapy is also showing promise across a range of neurological conditions. Svendsen, for instance, is testing a stem-cell treatment in people with amyotrophic lateral sclerosis, a progressive disease that destroys motor neurons and leads to paralysis. His team uses human neural progenitor cells to generate astrocytes that secrete neuroprotective growth factors. Rather than replacing neurons, he is helping the surviving ones stay alive longer. An early trial targeting the spinal cord showed modest slowing of progression on the treated side of the body3. And a phase 1/2a trial, this time targeting the motor cortex, is currently underway. Other groups, such as that of neurologist Letizia Mazzini at the University of Eastern Piedmont in Italy, are also moving forward with stem cells in amyotrophic lateral sclerosis. Her team is preparing a phase 2 trial of fetal neural-cell transplantation, building on protocols tested in multiple sclerosis.
For Alzheimer’s disease, Longeveron, a biotechnology firm based in Miami, is developing laromestrocel, a mesenchymal stem-cell therapy — cells derived from bone marrow that can differentiate into various cell types. Results from its 39-week phase 2a trial of 49 patients showed reduced brain atrophy, particularly in the hippocampus and temporal lobes, and signs of reduced inflammation after a single injection. “It was surprising to see such convincing data with the small sample sizes and relatively brief trial,” says Joshua Hare, the company’s chief scientific officer4. The US Food and Drug Administration has granted laromestrocel status as a regenerative medicine advanced therapy, allowing the company to pursue a streamlined phase 2b/3 trial.
Elsewhere, stem-cell trials are progressing in epilepsy, macular degeneration and spinal cord injury. For instance, Neurona Therapeutics, a biotechnology company in San Francisco, California, says it plans to conduct a phase 3 study to test NRTX-100, a regenerative therapy derived from human pluripotent stem cells that delivers GABA-secreting neurons to the brain to reduce seizures, for the treatment of drug-resistant epilepsy. Phase 1/2 results showed that 80% of participants reported seizure reductions of more than 75% at 7–12 months after receiving a low dose of NRTX-100.
Which cells work best?
Researchers are exploring the pros and cons of various stem-cell strategies. Embryonic stem cells can develop into all cell types, yet these raise ethical concerns about embryo destruction. Mesenchymal stem cells, such as those used by Longeveron, are valued for their immunomodulatory and anti-inflammatory properties. They can be sourced from one donor and used across many patients without triggering an immune response, says Hare. The advantage of induced pluripotent cells is that they are incredibly versatile, says Roger Hajjar, director of Mass General Brigham Gene and Cell Therapy Institute in Boston, Massachusetts. “Their flexibility is a huge advantage.” But it also carries higher risk of unpredictable immune responses. As a result, induced pluripotent cells often require more complex manufacturing and safety protocols. “And it currently remains unclear if they can integrate correctly into the brain circuitry, or address the inflammatory and vascular dysfunction components of neurodegenerative diseases,” Hare adds.
The waiting game
Another major challenge in neural stem-cell transplantation is time. Transplanted stem cells can take years to mature and integrate. Yet many clinical trials are designed with follow-up periods of up to 2 years, which could be too short to capture the full effect. Then there is the problem of permanence. With a pill, if there is a side effect, you could stop taking it, says Svendsen. But once stem cells are implanted, they are in for life. The irreversible nature of stem cell transplants raises ethical questions around informed consent and post-trial monitoring. If a sponsor company folds, or if the government stops funding a research project, trial participants would still be walking around with living grafts, and might not be appropriately followed up, he warns.
Cost and access are also major questions on the horizon. Stem cell therapies are not cheap. But if they offer long-lasting benefits from a single dose or a limited number of doses, they might ultimately prove cost-effective, says Rash. Scaling up production is another challenge, he adds. It is not just about the science, but about the systems that will deliver neurological stem-cell therapies.
Despite the complexities, researchers remain cautiously optimistic. Advances in gene editing, such as CRISPR-modified induced pluripotent cells that are more resilient or less likely to trigger rejection by the immune system, are already being explored, says Svendsen. And Mazzini points out that advances in automated cell manufacturing are making it easier to scale production. Meanwhile, artificial intelligence is beginning to have a role across the pipeline, from optimizing cell production to analyzing clinical trial data, she adds. Together with increased industry involvement, and broader acceptance of stem-cell therapy for neurological conditions, such developments are expected to accelerate progress in the years ahead.
What began decades ago as an ambitious idea is edging closer to clinical reality. Although there is still a long way to go, recent clinical trials suggest it could be feasible to repair the brain, the most complex organ of all. “I think it’s going to open up a whole world where we’ll see a lot more exciting science coming through,” says Tabar.
Natalie Healey, Freelance writer, London, UK.
GDNF, glial cell line-derived neurotrophic factor.
References
Tabar, V. et al. Nature 641, 978–983 (2025).
Sawamoto, N. et al. Nature 641, 971–977 (2025).
Baloh, R. H. et al. Nat. Med. 28, 1813–1822 (2022).
Rash, B. G. et al. Nat. Med. 31, 1257–1266 (2025).
(Sources: Nature)
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