Novel insights into the pathogenesis of cystinosis Podocyte dysfunction and zebrafish modeling

Cystinosis is a rare, incurable autosomal recessive lysosomal storage disease caused by mutations in the CTNS gene, which encodes the cystine transporter cystinosin, leading to lysosomal cystine accumulation in all cells of the body. Although cystinosis is a multi-systemic disorder, the kidneys are the first and the most severely affected organs. While cystinosis is an archetypal proximal tubular disorder, patients present with progressive glomerular dysfunction characterized by the presence of high-molecular-weight proteinuria and excessive shedding of podocytes into urine at an early disease stage. In the current project, we aim to explore the molecular mechanisms of glomerular disease in cystinosis using patient-derived and animal disease models. Our final aim is to restore the glomerular impaired phenotype using a pharmacological approach.