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Abstract: FR-PO602

Novel Therapy for Cystinuria Using Genetic Tools

Session Information

Category: Genetic Diseases of the Kidneys

  • 1202 Genetic Diseases of the Kidneys: Non-Cystic


  • Dakhakhini, Mohammed, University of Bristol Faculty of Health Sciences, Bristol, United Kingdom

Group or Team Name

  • Bristol Renal Group.

Available drug treatment for Cystinuria is still imposes huge disadvantages to patients through harmful side-effects. This fact necessitates the need for other therapeutic approaches without causing major side-effects. Cystinuria is caused by a mutation of b0,+AT (SLC7A9 ) or rBAT (SLC3A1) Proteins. Mutations result in the mis-localization of functioning channles at the plasma membrane (PM) leading to a disruption in cystine reabsorption that results in the accumulation of cystine stones. This research hypothesizes that repurposing established drug compounds to re-direct both proteins into the PM is a new and improved therapeutic approach.


In this study, we utilised constructed transduced human PTEC to investigate the localisation of b0,+AT and rBAT in wildtype and four mutated cell lines: p. Met467Thr, p. Thr216Met, p. Gly458Arg, and p. Asn254Thr using various imaging systems. Primary investigation was done using ICC/IF followed by Widefield Fluorescence Microscopy. Follow-up investigations were done using Confocal Microscopy and co-localisation analysis of obtained data. Findings were confirmed by TIRF Microscopy. Currently, the INCELL analyser is being used to optimise the LOPAC 1280 in these cell lines.


All localisation studies done using different imaging systems showed the same results. Firstly, both proteins were found to be trafficked together. Secondly, in the wild-type cell line, both proteins were located at the PM. Thirdly, in mutated cell lines, both proteins were trapped in the ER. Morphological changes of PTEC were supportive of the co-localisation studies.


Both proteins were trapped in the ER in all four mutants in contrary to wild-type cell line. These findings allow testing of LOPAC 1280 drugs to show their efficacy in re-locating proteins into the PM. Radiation testing will followed to confirm functionality of both proteins.