Study of Neurodegenerative Diseases Induced Stem Cells in Patients and Healthy Family Controls.

Neurological and neurodegenerative diseases have a major impact in families and in the national health service due to the lack in many cases of effective and long-lasting therapies. The lack of these therapeutic strategies is due in large part to the difficulty of modeling these pathologies in vitro. In fact, the impossibility of being able to cultivate human neurons in vitro has forced the use of animal cell models that do not adequately recapitulate the complexity of these human pathologies. For this reason it is necessary to proceed with the development of in vitro models of human origin that reproduce the molecular and biochemical characteristics of these diseases. The discovery of cellular reprogramming allowed the generation of pluripotent stem cells from the conversion of somatic cells taken from adult individuals. The proposing group already has great experience in generating iPS cells by reprogramming and in differentiating them into neurons and glias useful for neurological disease cellular studies. As an example, Dr. Broccoli's group has generated iPS cells from patients with Parkinson's disease and mutations in the OPA1 gene. The study of neurons differentiated by these iPS cells allowed to identify mitochondrial defects at the base of neuronal dysfunctions and to identify for the first time how the degeneration of dopaminergic neurons also depends on a moving mode of cell death called necroptosis. The investigators therefore propose to establish lines of iPS cells from patients with genetic mutations responsible for neurological and neurodegenerative diseases to generate neuronal and glial models in vitro for the study of pathological mechanisms and the validation of new future experimental therapies.