Parkinson's Disease (PD) is a highly complex neurodegenerative disorder. Its incidence rate among neurodegenerative diseases worldwide ranks second only to Alzheimer's disease (AD). The incidence rate of this disease among the elderly aged 65 and above is approximately 1%-2%. With the intensification of global population aging, it is estimated that the number of Parkinson's disease patients worldwide will exceed 14 million by 2040. The core pathological feature of Parkinson's disease is the significant and progressive degeneration of dopaminergic neurons in the substantia nigra region of the brain and their projections in the striatum. This degeneration leads to motor-related symptoms such as bradykinesia, muscle rigidity and resting tremor in patients, along with non-motor symptoms such as autonomic nerve dysfunction, mental problems and sleep disorders. These symptoms greatly reduce the quality of life of patients.

Currently, for Parkinson's disease, drugs such as levodopa (ʟ-dopa) can effectively relieve symptoms in the early stages of the disease, but their efficacy gradually diminuts over time, often accompanied by side effects such as movement disorders (involuntary movement). Cell therapy, especially by filling the large imagination with dopaminergic neurons, is considered promising to offer a more effective and less side-effect treatment option for patients with Parkinson's disease.

On April 16, 2025, two independent clinical trial papers were published in the top international academic journal Nature. These two studies respectively explored cell therapies based on human induced pluripotent stem cells (hiPSC) and human embryonic stem cells (hES). The results indicated that these therapies had good safety for patients with Parkinson's disease and initially demonstrated certain therapeutic effects. The achievements of these two studies mark a crucial step forward in the application of cell therapy in the treatment of Parkinson's disease.

Phase I/II trials of dopaminergic precursor cells derived from IPscs

In this clinical study, the research team from Kyoto University utilized CORIN+ dopaminergic precursor cells derived from HLA-matched human induced pluripotent stem cells (hiPSC). The trial protocol was a single-center, open-label phase I/II study, involving a total of 7 patients whose ages ranged from 50 to 69 years old. All patients received cell transplantation from bilateral putamen and were divided into a low-dose group (2.1-2.6×10⁶ cells per side) and a high-dose group (5.3-5.5×10⁶ cells per side). The follow-up period of the entire study was 24 months.

In terms of safety and tolerability, no serious adverse events or tumor formation were observed in the study. However, some patients experienced a worsening of mild motor disorders during the period of drug adjustment. In terms of immunosuppressive therapy, the patient was treated with tacrolimus. After 15 months of drug withdrawal, no rejection reaction was found. In terms of therapeutic effect evaluation, imaging examinations showed that the average intake of ¹⁸F-DOPA in the putamen area increased by 44.7%, among which the increase was more significant in the high-dose group. In terms of clinical scoring, among the 6 patients who continued to participate in the clinical trial to evaluate its effectiveness, 4 observed a reduction in Parkinson's disease-related motor symptoms without taking standard drugs, and 5 patients also observed a reduction in related motor symptoms while taking medication. The research team believes that iPSC transplantation is safe and may have therapeutic effects, but further studies are needed to optimize patient selection and dosage strategies.

Phase I trial of dopaminergic neurons derived from hES

In this clinical study, the research team from Memorial Sloan Ketterine Cancer Center and BlueRock Therapeutics (a wholly-owned subsidiary of Bayer) used dopaminergic precursor cells derived from human embryonic stem cells (hES). The research protocol was an open-label phase I trial. A total of 12 patients were included and divided into a low-dose group (0.9×10⁶ cells on each side) and a high-dose group (2.7×10⁶ cells on each side), and cell transplantation of bilateral pusin nuclei was performed.

In terms of safety and tolerability, the results of the primary endpoint (12 months) showed that no serious adverse events related to transplantation or immunosuppression occurred. During the 18-month follow-up, no tumors or transplant-induced movement disorders (GID) were found either. In terms of therapeutic effect evaluation, imaging examinations revealed an increase in the intake of ¹⁸F-DOPA in the putamen area through PET, and the increase was more significant in the high-dose group. In terms of clinical scores, the MDS-UPDRS III OFF score of patients in the high-dose group improved by an average of 23 points and decreased by 35% compared with the baseline level. In terms of immunosuppression, the patient received tacrolimus and glucocorticoid treatment one year after the operation, but no long-term maintenance was carried out. The research team believes that the safety performance of this cell therapy is good, providing support for future deterministic clinical trials.

The similarities between these two studies are as follows:

1. In terms of safety: Both clinical trials have confirmed good safety, with no transplantation-related tumors or serious complications observed.

2. Imaging results: The survival of transplanted cells and the activity of dopamine synthesis were all verified by ¹⁸F-DOPA PET imaging technology.

3. Dose-correlation: In terms of imaging manifestations and clinical scores, the improvement effect was more significant in the high-dose group.

4. Immunosuppressive regimens: Both studies adopted short-term immunosuppressive measures (with durations of 1 year or 15 months respectively), and neither reported long-term immune-related issues.

Overall, both of these clinical trials have verified the safety of using allogeneic (non-patient's own) stem cell-derived cell products for Parkinson's disease transplantation treatment and have initially demonstrated their efficacy. Among the two cell types, both hES cells and iPS cells have unique advantages: The therapeutic effect of hES cells is more stable, while iPS cells, due to HLA matching, may further reduce the risk of immune rejection. Future research needs to further verify its long-term efficacy through larger-scale double-blind controlled trials and optimize cell doses, transplantation strategies, and patient screening criteria.

China is at the forefront of the world in the field of stem cell therapy for systemic diseases

It is worth noting that in January 2025, the U.S. Food and Drug Administration (FDA) officially approved the investigational New drug application (IND) for the general-purpose IPSC-derived dopaminergic neural precursor cell injection independently developed by Shize Biotech, for conducting a registered clinical Phase I trial for Parkinson's disease in the United States. In addition, the FDA has granted Shize Biotech a special Exemption for its new Parkinson's disease drug. Immediately following this, in February 2025, the US FDA once again officially approved the investigational New drug application (IND) for the general-purpose IPSC-derived subtype neural precursor cell injection independently developed by Shize Biotech, to conduct a registration clinical trial for ALS in the United States. This marks China 's first IPSC-derived cell-derived new Drug receiving Orphan Drug Designation (Designation) from the U.S. FDA. Under the U.S. Orphan Drug Act, the drug will enjoy market exclusivity, accelerated review eligibility and special support policies.

Previously, Shize Biotech successfully completed in 2024 the only two national-level stem cell filing clinical research projects in China that were officially approved by the two national commissions and bureaus for the treatment of neurological diseases with clinical-grade IPSC-derived cells, targeting Parkinson's disease and ALS respectively. This includes the "first in China" clinical study on IPSC-derived cell therapy for Parkinson's disease completed by Shize Biotech (the clinical follow-up period has exceeded 12 months, no treatment-related adverse events have occurred, and the key efficacy indicators and multiple non-motor indicators of many trial patients have significantly improved). And the "world's first" clinical study on the treatment of ALS with IPSC-derived cells. These achievements indicate that China has reached a globally leading level in the development of clinical-grade IPSC-derived cell-based new drugs for the treatment of neurological diseases such as Parkinson's disease and ALS, and even holds a pioneering position globally in some fields.