Prostaglandin Analogs and Eupatilin as Treatments for Nephronophthisis.

INTRODUCTIONPrimary cilia (PCs) are sensory antennae that are present on the majority of quiescent vertebrate cells where they mediate key signaling during development and in response to environmental stimuli. Defects in PCs result in a group of heterogeneous inherited disorders with overlapping phenotypes, called ciliopathies. Nephronophthisis is an autosomal recessive tubulointerstitial kidney ciliopathy with > 25 identified genes called . Presently, no treatment exists beyond supportive care and kidney transplant, underscoring the need for novel therapies.METHODSUsing a phenotypic screening approach in cultured cell lines, we previously identified prostaglandin analogues as candidate therapeutic molecules based on their ability to rescue ciliogenesis defects in kidney tubular cells from patients with . Here, we investigated the potential beneficial effects of ROCK inhibitor and Eupatilin, similarly identified by other groups in different contexts, in kidney cells from patients with and those with as well as in a zebrafish mutant line ().RESULTSEupatilin partially rescued -associated ciliogenesis defects. Transcriptomic analyses pointed out that cell cycle progression was inhibited by Eupatilin, likely explaining its broad effects on cilia assembly. Interestingly, though ciliary defects also observed in patient cells were rescued by both prostaglandins and Eupatilin, only prostaglandin analogues were able to reduce pronephric cysts size in the used zebrafish model.CONCLUSIONOur study indicates that these molecules can show beneficial effects across genetic contexts and shed light on their potential as therapeutic interventions for nephronophthisis.KEYWORDSEupatilin, ciliopathies, kidney, nephronophthisis, primary cilia, prostaglandins© 2025 International Society of Nephrology. Published by Elsevier Inc.