On January 7, 2025, China's first induced pluripotent stem cell (iPSC)-derived cell therapy for the treatment of Parkinson's disease made breakthrough progress at Shanghai City Dongfang Hospital.

According to information released by Shanghai City Oriental Hospital on January 7, the hospital cooperated with Shize Biomedical (Suzhou) Co., Ltd. to conduct research to regenerate healthy nerve cells in vitro through human autologous iPSC to treat Parkinson's disease. At present, the exercise ability and quality of life of many subjects have significantly improved compared with before cell therapy. This is also the first time in China that subtype specialized dopaminergic neural precursor cells derived from human autologous iPSC have been used as alternative transplantation for the treatment of Parkinson's disease. Studies have shown good clinical treatment safety and effectiveness.

Induced pluripotent stem cell technology has great potential in treating degenerative diseases of the nervous system

Parkinson's disease (PD) is one of the most serious neurological diseases, but there is currently no effective treatment. The emergence of human induced pluripotent stem cells (iPSC) provides an unprecedented opportunity to understand the pathogenic mechanisms of PD and identify new therapies.

Parkinson's disease (PD) is the second most common neurodegenerative disease in humans. The disease is caused by a specific loss of dopaminergic (DA) neurons in the substantia nigra dense (SNpc) of the midbrain. Parkinson's disease is characterized by motor symptoms such as tremors, muscle rigidity and bradykinesia, but is also associated with cognitive impairment, sleep disorders, depression and reduced sense of smell. Currently, various methods have been used to treat Parkinson's disease.

Drug therapy, deep brain stimulation (DBS), gene therapy and cell therapy are currently available treatments. Levodopa, dopamine agonists and monoamine oxidase-B (MAO-B) inhibitors are representative drugs used to increase low dopamine levels in PD patients. These drug therapies can improve patients 'exercise symptoms, but long-term treatment with levodopa or dopamine agonists may worsen patients' symptoms due to drug tolerance and neurotoxicity. In addition, nausea, daytime sleepiness and edema are also possible side effects of these treatments.

Deep brain stimulation (DBS) is a surgical procedure that provides electrical stimulation to relieve symptoms by inserting electrodes into motor control areas of the brain, such as the subthalamic nucleus (STN) or the interior of the globus pallidus (GPi). Patients who develop drug resistance due to long-term drug treatment may benefit from DBS. The advantage of DBS is that patients can reduce drug doses and turn electrodes on or off as needed. Because the brain areas where DBS is implanted are also involved in emotions, side effects such as mood disorders and manic reactions can lead to mental problems.

Currently, these therapies may improve the symptoms of Parkinson's disease, but a fundamental cure has not yet been found. Therefore, people are studying various treatment methods. Epidemiological surveys show that the prevalence rate of people over 65 years old in my country is 1.7%, similar to that of European and American countries. It is estimated that by 2030, the number of Parkinson's disease patients in my country will rise to 4.94 million, accounting for almost half of the global number of Parkinson's disease patients.

In recent years, with scientists 'in-depth research on nervous system plasticity and nerve regeneration, stem cell therapy has become an international research hotspot.

The first subject's motor function was significantly enhanced 12 months after surgery

Currently, many stem cell types are used in clinical trials, including mesenchymal stem cells, neural stem cells, embryonic stem cells and induced pluripotent stem cells (iPSC).

Wu Jingwen, director of the Functional Neurosurgery Department of Shanghai City Oriental Hospital, mentioned in an interview with the media: "iPSC converts ordinary somatic cells into stem cells through genetic reprogramming and differentiates into a variety of different functional cell types, including dopamine neurons. For cell replacement transplantation therapy, it is a potential source of cells for the treatment of Parkinson's disease using cell transplantation therapy."

There have been many preclinical studies abroad on iPSC cell-derived dopaminergic progenitor cells for the treatment of Parkinson's disease. Primate trials have shown that iPSC cells are safe and effective in treating Parkinson's disease, and the results have important guiding significance for the clinical transformation of cell transplantation therapy.

Based on this, Shanghai City Dongfang Hospital cooperated with Shize Biological Company. With academic and ethical approval from the hospital, and approval from the National Health Commission and the State Food and Drug Administration, the project "Clinical Research on the Treatment of Parkinson's Disease Using iPSC-differentiated Dopaminergic Nerve Precursors" was established and implemented, making it the first national-level registered clinical research project in China for the treatment of Parkinson's disease.

The research team jointly developed an injection of dopaminergic neural precursor cells derived from autologous iPSC. The first subject was a patient with Parkinson's disease for many years and almost lost his ability to exercise. The team delivered dopaminergic neural precursor cells to a specific part in the brain-the putamen through stereotactic brain transplantation.

"The transplanted cells complement the missing function of dopaminergic cells in the patient's brain by verifying the value in the shell and secreting dopamine, thereby exerting their therapeutic effect." Wu Jingwen said that the effectiveness analysis of the patient's 12 months after surgery showed that his motor function was significantly enhanced, and he could complete walking, running, using chopsticks, writing, etc. The daily "on period"(i.e., the validity period of the drug) was extended, and the "off period"(i.e., the drug expiration period) was shortened and improved by about 2 hours/day.

"This product is from the patient's own source, is non-immunogenic, and will not cause immune rejection. Therefore, during the research process, there is no need to use immunosuppressants for treatment, let alone HLA (human leukocyte antigen) typing." Wu Jingwen added.

Liu Zhongmin, honorary president of Shanghai City Dongfang Hospital and chief scientist of Shanghai Tongjin Stem Cell Technology Co., Ltd., said that before the team launched this project, only one foreign patient worldwide had used laboratory-level autologous iPSC to induce differentiation of dopaminergic neural precursors to treat Parkinson's disease, and obtained positive preliminary clinical research results, which were published in the 2020 New England Journal.

"The results of this project will help assess the safety of using human iPSC-differentiated dopaminergic neural precursor cells to treat Parkinson's disease, analyze its impact on the efficacy of individual subjects, drug formation and future clinical application potential." Liu Zhongmin mentioned that this therapy may reverse the worsening course of Parkinson's disease and add new strategies to the clinical treatment of Parkinson's disease in my country.