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During the congress, E-Posters will be accessible to all participants on the congress website 24/7, as well as in the E-poster stations in the congress center.
Preparing your E-Poster
Please review the E-Poster format requirements carefully when preparing your E-Poster. Should your E-Poster not meet the mentioned requirements, it may not be displayed as described above.
E-Poster Submission Deadline
Please prepare and upload your E-Poster no later than March 14, 2026 11.59PM CET. After this date, you will no longer be able to prepare and upload your E-poster and it will not be displayed and accessible on the congress website.
Please follow the instructions below to input your abstract title.
Abstract titles should be brief and reflect the content of the abstract.
Autosomal dominant polycystic kidney disease (ADPKD) is the leading genetic cause of end-stage renal failure, affecting over 12 million individuals globally, with approximately 600,000 cases in the U.S. alone. It results primarily from loss-of-function mutations in PKD1 (accounting for 77% of cases) and PKD2 (15%). These mutations disrupt polycystin-1 (PC1) and polycystin-2 (PC2) protein complexes, impairing their proper maturation and ciliary trafficking in kidney epithelial cells, thus leading to cyst formation and renal failure. Our previous work has revealed the importance of PC1 dosage in modulating polycystic kidney and liver disease in vivo.
The primary aim of this research was to investigate the therapeutic potential of previously described chemical chaperones to enhance the biogenesis and ciliary trafficking of mutant PC1 protein (carrying human ADPKD pathogenic mutations) and alleviate disease progression in vivo.
We used our recently developed PC1-R2216W hypomorphic mutant cell model to test the effectiveness of chemical chaperones through in vitro biochemical assays assessing protein biogenesis, GPS cleavage, and ciliary localization. We used the Pkd1R221W/flox; Pax8-rtTA; TetO-Cre mouse model to examine the effect of chemical chaperones in vivo. We performed similar experiments for another PC1 mouse model mutant we have recently developed i.e. Pkd1-E2771K, that displays a complete GPS cleavage defect.
Treatment with chemical chaperones significantly improved the biogenesis, GPS cleavage and ciliary trafficking of mutant PC1-R2216W protein. Furthermore, in vivo studies demonstrated that chaperone treatment slowed down disease progression compared with un-injected control. Importantly, there was no therapeutic effect for chaperone treatment in models completely lacking PC1, underscoring its mechanism of action through stabilizing partially functional PC1 proteins.
The study highlights the utility of chemical chaperones in the context of ADPKD hypomorphic backgrounds where residual by improving protein folding and trafficking of pathogenic PC1 variants. The allele-dependent effectiveness of PBA indicates its potential as a personalized treatment strategy, specifically benefiting patients with hypomorphic mutations. Further clinical investigations are warranted to validate these promising preclinical outcomes.
