Modelling Friedreich Ataxia in human iPSC-derived cerebellar organoids

This project will establish three-dimensional models of the human cerebellum in a dish from stem cells derived from FA patients. This project aims to create three-dimensional models of the human cerebellum called ‘organoids,’ using induced pluripotent stem cells from patients with FA. This innovative method will allow us to understand better why nerve cells in the cerebellum are particularly vulnerable to FA and use this insight to test potential therapeutic treatments for FA. Human induced pluripotent stem cells (iPSCs) are obtained from individuals’ skin cells by a process known as reprogramming and resemble stem cells present in the developing human embryo that are capable of turning into any cell type in the body. Coaxing iPSCs obtained from patients into brain cells allows studying living human nerve cells from affected patients in the laboratory and recapitulates early events that lead to disease in the relevant, vulnerable cell types. The Becker group is one of the few worldwide that has set up a protocol to use human iPSCs to produce nerve cells of the cerebellum and grow tissue-like cerebellar organoids. Dr. Becker proposes to produce cerebellar organoids from FA patient iPSCs and compare these to organoids generated from healthy controls. This will shed light on the molecular and cellular processes that go awry in the FA cerebellum and that might be amenable to therapeutic correction. Overall, this study will provide valuable insights into how FA affects the cerebellum and could help develop better treatments for this disease.