Jun Takahashi is a professor and deputy director of the Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan. He graduated from the Kyoto University Faculty of Medicine in 1986 and thereafter started his career as a neurosurgeon at Kyoto University Hospital. After he earned his Ph.D. from the Kyoto University Graduate School of Medicine, he worked as a postdoctoral research fellow at the Salk Institute (Dr. Fred Gage), CA, U.S.A., where he started research work on neural stem cells. After returning to Kyoto University Hospital, he conducted functional neurosurgery including deep brain stimulation and also research work on stem cell therapy for Parkinson’s disease. In 2012, he became a full professor at CiRA, pursuing stem cell therapies for Parkinson’s disease patients. As a physician-scientist, he has laid the groundwork for the clinical application of iPS cells and started the world’s first clinical trial for Parkinson’s disease using iPS cells in 2018.
Human iPS cell-derived dopaminergic neurons function in a primate Parkinson’s disease model
Human induced pluripotent stem cells (iPSCs) can provide a promising source of midbrain dopaminergic (DA) neurons for cell replacement therapy for Parkinson’s disease (PD). Towards clinical application of iPSCs, we have developed a method for 1) scalable DA neuron induction on human laminin fragment and 2) sorting DA progenitor cells using a floor plate marker, CORIN. The grafted CORIN+ cells survived well and functioned as midbrain DA neurons in the 6-OHDA-lesioned rats, and showed the minimal risk of tumor formation. In addition, we performed a preclinical study using primate PD models. Regarding efficacy, human iPSC-derived DA progenitor cells survived and functioned as midbrain DA neurons in MPTP-treated monkeys. Regarding safety, cells sorted by CORIN did not form any tumors in the brains for at least two years. Based on these results, we have started a clinical trial to treat PD patients at Kyoto University Hospital in Kyoto, Japan, in 2018. The trial evaluates the safety and efficacy of transplanting human iPS cell-derived DA progenitors into PD patients’ putamen. We implant approximately 5 million cells to each of 7 patients and observe for 2 years. By showing these results, I will discuss how we can cross the valley of death.