Translational View on Therapeutic Strategies and Upcoming Issues: Stem Cell and Brain Organoid Approaches for Parkinson’s Disease Therapy

There are currently no disease-modifying therapies for Parkinson’s disease (PD), and the available therapies only relieve the symptoms and not disease progression. Cell replacement therapy to restore the degenerating neurons is a promising approach to treating advanced stages of PD. The idea behind cell therapy dates back to the 1970s, when the first transplantation of fetal ventral mesencephalic tissue was performed on neurotoxic animal models of PD and showed promising motor recovery and graft survival. Based on this early proof of concept, several other cell types from different sources—e.g., embryonic stem cells or induced pluripotent stem cells—were tested and used in several preclinical studies, leading to transplantation into a small number of human subjects. After proving the safety of the method and the overall positive clinical outcome, several clinical trials were organized in Europe, in the United States, and in the rest of the world. In this chapter, we describe the story of modern stem cell-based clinical trials for the treatment of PD and highlight the successes and limitations of these approaches as well as the key discoveries associated with it. Part of the chapter is also dedicated to the use of brain organoids as a new promising interface between in vitro and in vivo models, which could lead to the development of novel disease-relevant insights and new promising therapeutic avenues in the near future.