Phenotypic impact of FXN gene splicing reprogramming in Friedreich Ataxia cells and mice

Friedreich Ataxia (FRDA) is a rare, progressive neurodegenerative disorder caused by a GAA trinucleotide repeat expansion in the first intron of the FXN gene, resulting in reduced expression of frataxin, a mitochondrial protein essential for iron-sulfur cluster biogenesis and cellular energy metabolism. Frataxin deficiency leads to mitochondrial dysfunction and progressive neurological and cardiac manifestations, with cardiomyopathy representing a major cause of morbidity and mortality. The research program aims to investigate the molecular and functional consequences of a novel therapeutic strategy designed to increase endogenous frataxin expression through reprogramming of FXN pre-mRNA alternative splicing. [...]