Fig. 2

Visual representation of FRDA therapeutics investigated in FRDA iPSCs and their derived models. FRDA iPSCs have been utilised to generate phenotypically relevant cell models, providing a valuable platform for preclinical drug screening and development. Different therapeutic approaches have been studied using these novel models, with this figure detailing their approximate site of action within the cell. Modulation of the pathological FRDA gene has been investigated with epigenetic therapy, gene editing and other compounds such as polyamide FA1, antisense oligonucleotides and duplex RNA. Other approaches involve targeting the RNA Pol II enzyme and FXN mRNA transcript, as well as the delivery of exogenous plasmids carrying relevant FXN-expressing genetic information. As frataxin localises to the mitochondria, several therapeutics also act at the mitochondria to deal with the downstream consequences of frataxin deficiency, including reactive oxygen species (ROS) generation, iron accumulation and mitochondrial-activated apoptosis. Figure created with BioRender.com