Stem Cell Therapy Shows Promise in First Human Parkinson’s Disease Trial

A landmark Phase I/II clinical study led by researchers at Skåne University Hospital and Lund University has shown that transplanting stem-cell-derived dopamine progenitor cells into the brain is feasible. Eight patients with Parkinson’s disease (PD) received transplants of STEM-PD, a cryopreserved, off-the-shelf dopaminergic progenitor product derived from human pluripotent stem cells. The three-year Phase I/II, open-label, multicenter, single-arm, dose-escalation study identified no serious side effects linked to the transplanted cells during the first year of follow‑up.

“The possibility of replacing dopamine neurons that are lost in Parkinson’s disease has been a long-standing goal in the field,” said Malin Parmar, professor of cellular neuroscience at Lund University, and lead of the STEM-PD program. “The findings represent an important milestone for regenerative medicine approaches in Parkinson’s disease and support continued clinical development of stem cell-based therapies.”

Results from the study were reported by Parmar and colleagues in Nature Medicine. In their paper, titled “Human embryonic stem cell-derived dopaminergic cells for Parkinson’s disease: a Phase I/II open-label trial,” the team wrote, “In conclusion, particularly in the context of other recently published trials using human PS cell-derived dopaminergic cell therapies for PD, these findings further support the continued development of this therapeutic approach, including evaluation of the STEM-PD product in larger patient cohorts.”

Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s disease, the authors wrote. In Parkinson’s disease, patients lose nerve cells in the brain that produce dopamine, which leads to symptoms such as slowness of movement, stiffness, gait disturbance, and tremor. “The hallmark pathology of PD involves progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the subsequent loss of their projections to the striatum,” the team explained. Current treatments are medications that replace the lost dopamine, but over time these medications often become less effective and cause side effects.

“Intracerebral transplantation of stem cell-derived dopaminergic progenitors to replace lost endogenous dopaminergic neurons offers a new potentially restorative therapeutic approach for PD,” the investigators continued. Scientists have been working to develop standardized and scalable dopamine cell therapy products derived from pluripotent stem (PS) cells, including human embryonic stem (ES) cells and induced PS (iPS) cells, they noted. “Several such products are now in clinical development … with early safety and feasibility data emerging.”

The transplanted stem cell-based dopamine nerve cell product tested in the newly reported trial is designed to replace the cells that produce dopamine, and the goal is that after being transplanted, the transplanted cells will mature into new dopamine-producing nerve cells in the brain. The STEM-PD trial aimed to evaluate the safety, tolerability, and feasibility of intraputaminal transplantation of STEM-PD in patients with moderately advanced PD.

Eight individuals with Parkinson’s disease received the transplanted cell product at two different doses, followed by 12 months of immunosuppression to prevent graft rejection. All patients were treated at Skåne University Hospital. Seven participants completed 12-month follow-up, and one participant died from a pulmonary infection that was not directly related to the cell product.

The surgical procedure was generally well tolerated, and no graft-induced involuntary movements were observed in the transplanted participants. Clinically, patients remained stable. Imaging using dopamine PET scans provided early indications of graft survival at both 6 and 12 months post-transplantation. Six of the seven participants substantially reduced their dopaminergic medication, a result that will be evaluated over time. In their paper, the team wrote in summary, “This Phase I/II clinical trial involving the bilateral intraputaminal transplantation of the STEM-PD dopaminergic progenitor cell product demonstrates its feasibility with no unexpected safety concerns from the cell product.”

Roger Barker, MD, professor of clinical neuroscience at the University of Cambridge, clinical lead of STEM-PD and clinical PI at the U.K. site, said: “This represents an exciting new departure on repairing the brain of individuals with Parkinson’s using dopamine cells- an approach pioneered in Lund some 40 years ago using fetal dopamine cells. The STEM-PD trial harnessing the expertise of scientists and clinicians from Lund and Cambridge has enabled us to undertake and deliver on one of the first ever stem cell-derived dopamine cell therapies for patients with Parkinson’s, and we hope this will be the beginning of an exciting new programme that may ultimately benefit the wider Parkinson’s community.”

Gesine Paul-Visse, MD, professor in neuropsychiatric research and lead PI at Skåne University Hospital, said, “Reaching this primary endpoint and being able to show that the cell product is safe is a great achievement for this trial, our team, the participating patients, but also for all patients suffering from Parkinson’s disease. We are hopeful that the early signs of cell survival and clinical improvement we observe will continue to increase over time and are excited to continue the development of this cell therapy.”

The STEM-PD research team will now continue the long-term follow-up of the participants to further evaluate safety, graft function, and clinical benefit. “Secondary and exploratory outcomes will evaluate the course and efficacy of clinical features, the survival of grafted dopaminergic cells at 36 months as well as additional safety signals occurring between 12 and 36 months and any dose–response effects,” the investigators stated. “Further evaluation of the grafts up to 36 months will determine whether the implanted cells continue to grow, mature and reinnervate the putamen after 12 months.”

STEM-PD builds on decades of research in dopamine cell replacement therapy for PD at Lund University and pioneering work in translation of pluripotent stem cell technology from experimental studies into clinical evaluation. The STEM-PD trial is the first pluripotent stem cell trial approved in Sweden and the first for PD in Europe. “The initiation and execution of this clinical trial have only been possible through close collaboration between scientists, clinicians, GMP manufacturing teams, regulatory experts and, most importantly, the participating patients,” concluded Parmar. In their report, the authors stated, “The STEM-PD trial adds further important confirmatory and complementary evidence to the recently reported feasibility and short-term safety of PS cell-derived dopaminergic progenitor transplantation in PD.”

The academic Phase I/IIa trial was conducted in collaboration with Novo Nordisk. Cellular Intelligence, a Boston-based company, recently acquired the STEM-PD program and will lead its next phase of clinical development, including a planned Phase II trial. The STEM-PD cells and their continued development hold IND clearance with FDA Fast Track Designation, and Cellular Intelligence aims to advance the program through Phase III to market approval.

STEM-PD is an academic European clinical translation initiative, focused on developing stem cell-based therapies for Parkinson’s disease. The program is led from Lund University with partners from Skåne University Hospital, Cambridge University Hospital, and University College London and combines expertise in stem cell biology, GMP manufacturing, neurosurgery, clinical neurology, and regenerative medicine to advance pluripotent stem cell-derived dopamine neuron therapies toward clinical application.

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