What Recent research has raised the question whether Parkinson's disease can arise in the nerve cells of the gut and spread from there to the brain. We propose a novel approach for addressing this by growing nerve stem cells isolated from standard gut biopsies from Parkinson's disease patients and healthy controls. This will enable us to determine whether the disease affects gut nerve cells from PD patients. By growing these nerve cells in the laboratory, we will be able to closely study the disease mechanisms and to test potential therapeutic strategies, which could prevent the disease from spreading to the brain. Why Parkinson's disease is a neurological disorder, which despite decades of research, we do not fully understand the disease mechanisms behind. We therefore only have treatments, which can temporarily alleviate the symptoms, but none that can slow down or prevent the disease from developing. Parkinson's disease affects not only areas of our brain essential for movement, but also many other parts of our nervous system. This includes the so called enteric nervous system, which surrounds and controls our gut. Recent research indicates that the disease can arise in the enteric nervous system and spread from there to the brain. This idea is mainly based on research studies on deceased patients and animal models and has not yet been verified in living patients. How In this project, we will obtain nerve stem cells from the enteric nervous system using standard gut biopsies taken from Parkinson's disease patients and healthy controls. This technique has been established for other diseases related to the enteric nervous system, but never applied to Parkinson's disease. From these nerve stem cells, we will grow live human enteric nerves in the laboratory and study their disease-related characteristics. This will provide a unique chance to explore how the disease develops over time and allow us to therapeutically target promising pathways to potentially hinder the spread of the disease to the brain. SSR The project will allow us to generate human Parkinson's patient specific nerve cells, which can be grown in the laboratory and applied in a variety of functional assays. These nerve cells can help address the role of the enteric nervous system in the development of Parkinson's disease and can potentially in the future enable direct studies of how environmental factors might influence the disease. Addressing the role of the ENS in PD pathogenesis could vastly improve our understanding of the disease mechanisms and potentially pave the way for new therapeutic solutions, which can prevent the disease from developing.