Positive Preliminary Results From Phase 1 Trial of Dopaminergic Neuron Graft for Parkinson’s Disease

An open-label phase 1 clinical trial investigated bilaterally grafting cryopreserved off-the-self dopaminergic neuron progenitor cell products, such as bemdaneprocel, derived from human embryonic stem cells, for the treatment of Parkinson’s disease (PD). The results were published in Nature.

The primary objective was to assess the safety and tolerability after 1 year of bemdaneprocel transplantation into the putamen among two cohorts: low dose (0.9 million cells; n=5) and high dose (2.7 million cells; n=7). All 12 participants received 1 year of immunosuppression to prevent graft rejection.

The study’s primary endpoint was the incidence of serious adverse events (SAEs). Safety was defined as meeting all the following criteria: no more than two participants per cohort experiencing two or more SAEs related to surgery, transplanted cells, or immunosuppression; no more than two developing tumors or abnormal tissue growth linked to the transplanted cells; no more than two experiencing life-threatening brain hemorrhages; and no more than one death per cohort.

At 12 months post-transplant, predefined safety criteria for the primary outcome were met. Two SAEs occurred: one low-dose participant was hospitalized briefly with COVID-19, and one high-dose participant had a seizure within 24 hours of surgery, extending their hospital stay by 1 day.

The seizure was treated successfully with a 2-month course of levetiracetam, with no recurrence. There were no deaths, no SAEs related to the transplanted cells or immunosuppression, and no evidence of tumors, abnormal tissue growth, or brain hemorrhages on MRI.

Eighteen months after grafting, increased 18Fluoro-DOPA uptake in the putamen indicated graft survival. Secondary and exploratory clinical outcomes showed either improvement or stability, including an average 23-point improvement in Movement Disorder Society Unified Parkinson’s Disease Rating Scale Part III OFF scores in the high-dose group. No graft-induced dyskinesias were observed. These findings support the treatment’s safety and encourage further clinical studies.

“Our findings should be interpreted carefully within the context of a small and unblinded safety and tolerability study that achieved its primary outcome and was not designed to evaluate efficacy based on clinical outcomes. Despite this, the possible improvement in PD symptoms at 18 months after transplantation may translate in future trials to an important finding,” the researchers concluded.

Reference

Tabar V, et al. Nature. 2025. Published online April 16, 2025. doi:10.1038/s41586-025-08845-y