Following intensive efforts since their discovery little more than 10 years ago, cell replacement therapy using induced pluripotent stem (iPS) cells is now becoming reality. However, there remain several obstacles in the translation of basic research to clinical application, obstacles known as the "Valley of Death". With regards to regenerative medicine using iPS cells for Parkinson's disease, we have developed a method for the 1) efficient induction of dopaminergic neurons from human iPS cells and 2) sorting dopaminergic progenitor cells using a floor plate marker, CORIN. The grafted CORIN+ cells survived well and functioned as midbrain dopaminergic neurons in the Parkinson's disease model rats and monkeys, and showed minimal risk of tumor formation. Based on these results, we performed a pre-clinical study using a clinical-grade iPS cell line and finally started a clinical trial to treat Parkinson's disease patients in August 2018. Here, I discuss the key issues to crossing the Valley of Death: scientific rationale, pre-clinical study, and clinical trial.
Keywords: Clinical trial; Dopaminergic neuron; Induced pluripotent stem cell; Parkinson's disease; Translational research; Transplantation.
© 2020 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.