On February 13, 2025, a team of researchers at Harvard Medical School published a compelling research paper in Cell Stem Cell, It is entitled "Pre-clinical safety and efficacy of human induced pluripotent stem cell-derived products for autologous cell therapy. in Parkinson's disease."

The study presents preclinical data on the safety and efficacy of autologous cell therapy based on human induced pluripotent stem cells (hiPSC) for Parkinson's disease, on which a clinical trial will be conducted in eight patients with Parkinson's disease.

In this preclinical study, the research team used somatic cell reprogramming to generate multiple clinically-grade human induced pluripotent stem cells (hiPSC) from newly biopsied fibroblasts from four patients with intermittent Parkinson's disease and differentiated them into midbrain dopaminergic cells (mDAC) using an optimized 21-day regimen.

The research team conducted a rigorous evaluation of the cells, including whole genome/exome sequencing, RNA sequencing, and in vivo studies, including efficacy studies and a 39-week safety study in mice that complied with Quality Management Practices for non-clinical Studies of drugs (GLP).

The results showed that:

1. Security:

In a GLP-compliant mouse safety trial up to 39 weeks, transplanted HIPSC-derived mDAC demonstrated an extremely high safety profile, with no toxicity, adverse reactions, or tumor formation in the mice during an observation period of 9 months. At the same time, in PD animal models, most transplant groups showed significant improvements in motor function. However, the study also found that different patient-derived cells were somewhat different in improving animal movement disorders, a finding that suggests the need to consider individual differences in autologous cell therapy in the future to further optimize treatment strategies.

2. Difference in curative effect

In animal models of PD, most transplant groups showed significant improvements in motor function. mDAC transplants from three patients restored motor function in mice by 70 to 85 percent and dopaminergic fiber density by 60 percent of normal levels. One patient's mDAC failed to improve behavioral outcomes in the mice. This suggests that there are significant differences in the efficacy of HiPSC-derived mDAC in different patients in the mouse model, and this finding suggests that individual differences need to be considered in future autologous cell therapy to further optimize treatment strategies.

Based on these prospective data, the research team has planned to initiate a phase 1 clinical trial of autologous cell therapy, with plans to enroll eight patients with Parkinson's disease in 2025. This trial will focus on evaluating the safety and initial efficacy of the cells after transplantation, laying the foundation for future large-scale clinical applications.

At present, the clinical trial has been officially launched, but no specific preliminary results have been announced or the expected timing of publication. Typically, preliminary data from a Phase 1 clinical trial may be available within six to 12 months of trial initiation, depending on the progress of data collection and analysis.

Advances in Parkinson's disease research in China

1. The clinical research of the first IPSC-derived cell therapy for Parkinson's disease in China has made a breakthrough

In January 2025, the team of Professor Liu Zhongmin of Shanghai Oriental Hospital and Shize Biology jointly carried out the first clinical research on IPSC-derived cell therapy for Parkinson's disease in China and made a breakthrough.

In this study, the research team jointly developed autologous dopaminergic neural progenitor cell injection from iPSC, and delivered the cells to a specific part of the patient's brain, the putamen, through brain stereotactic transplantation. This type of transplantation can effectively replace the missing function of dopaminergic cells in the patient's brain. After 12 months of participation in the clinical trial, the participants' motor ability and quality of life improved significantly, and the Parkinson's disease scale score decreased by more than 20 points.

2. CDE approved the first clinical trial of human midbrain dopaminergic neuroprecursor cell injection in China

On December 20, 2024, the Center for Drug Evaluation (CDE) of the State Drug Administration approved the clinical trial of the first induced pluripotent stem cell (iPSC) -derived cell candidate UX-DA001 injection (human midbrain Dopaminergic neuroprogenitor cell injection) for the treatment of primary Parkinson's disease in China.

UX-DA001 injection is based on the innovative multi-potent stem cell technology platform, including high-throughput stem cell differentiation lineage tracer platform, high-efficiency neural differentiation technology platform and iPSCs reprogramming technology platform, which can differentiate high-purity, high-stability and high-efficiency human midbrain dopaminergic neural precursor cells.

3. Xuanwu Hospital of Beijing Capital Medical University held an efficacy evaluation meeting

In November 2024, Xuanwu Hospital of Capital Medical University held an evaluation meeting on the efficacy of iNSC-DAP (induced dopaminergic neuroprecursor cells derived from neural stem cells) in the treatment of the first patient with Parkinson's disease 12 months after treatment.

The first patient had been suffering from Parkinson's disease for 8 years before surgery, and had obvious motor complications. In the opening period (the state when the drug takes effect and the symptoms improve), she could still move, but in the closing period (the state when the drug effect disappears and the symptoms worsen), she could not stand alone or take care of herself. After iNSC-DAP treatment, the patient could stand and walk alone one year after surgery, and the postural stability and overall quality of life were significantly improved. Imaging analysis showed that the transplanted dopaminergic nerve cells successfully survived and released neurotransmitters in the patient's brain, repairing damaged nerve function and confirming the significant efficacy of iNSC-DAP therapy. In addition, the patient did not have any serious adverse reactions after surgery, which further confirmed the safety of this treatment.

These studies not only confirm the safety and efficacy of stem cell therapy, but also provide a new direction for the treatment of Parkinson's disease. In the future, with the development of more clinical studies and the continuous optimization of technology, stem cell therapy is expected to become one of the mainstream treatments for Parkinson's disease, fundamentally improving patients' symptoms and delaying disease progression.