Preclinical evaluation of novel targets for FRDA cardiomyopathy

Heart disease is a major cause of death in Friedreich ataxia (FA), driven by dysfunction across various heart cell types. Ms Li and her mentor Dr Jarmon Lees have used stem cells from FA patients to grow key heart cells — the beating heart cells (cardiomyocytes), vascular cells (endothelial cells and smooth muscle), and structural support cells (fibroblasts) – and observed significant abnormalities compared to healthy controls. FA heart cells beat more slowly and form weaker blood vessels, and 3D heart tissues engineered from these cells show increased cell death and impaired function. To understand the underlying causes, Ms Li analyzed messenger RNA (mRNA) levels and identified eight RNAs significantly elevated in FA cells. These RNAs are linked to cellular damage and mitochondrial dysfunction but have not been studied in FA before. This PhD project aims to explore whether reducing these RNAs can reverse heart cell damage. Promising candidates will be tested in 3D heart tissue models and FA mouse models to evaluate their potential to restore heart function. This research could lead to new therapeutic targets for FA-related heart disease.