Correcting Cell-Autonomous Neuroinflammatory Phenotypes in Friedreich’s Ataxia Microglia Using iPSC-Based Approaches

The project of Dr. Stefano Stifani, and Co-PI Dr. Massimo Pandolfo’s project will investigate the role of microglia, the brain’s immune cells, in Friedreich’s ataxia (FA). Using patient-derived stem cells, the team has developed lab-grown microglia to study the changes caused by the FA mutation. Early findings suggest that FA microglia are inherently inflammatory, with overactive NLRP3 inflammasomes, including the NLRP3 inflammasome, that can release toxic molecules harmful to neurons. The study has two main goals: first, to characterize the inflammatory behavior of FA microglia and confirm their potential to damage neurons; second, to test drugs that block the NLRP3 inflammasome-mediated inflammation and evaluate whether reducing inflammation can protect neurons. This research could provide key insights into how microglia contribute to disease progression and may reveal a promising new approach to slow or prevent neuron damage in FA.