Cystine Growth Inhibition Through Molecular Mimicry: a New Paradigm for the Prevention of Crystal Diseases
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Cystinuria is a genetic disease marked by recurrent kidney stone formation, usually at a young age. It frequently leads to chronic kidney disease. Treatment options for cystinuria have been limited despite comprehensive understanding of its genetic pathophysiology. Currently available therapies suffer from either poor clinical adherence to the regimen or potentially serious adverse effects. Recently, we employed atomic force miscopy (AFM) to identify l-cystine dimethylester (CDME) as an effective molecular imposter of l-cystine, capable of inhibiting crystal growth in vitro. More recently, we demonstrated CDME’s efficacy in inhibiting l-cystine crystal growth in vivo utilizing a murine model of cystinuria. The application of AFM to discover inhibitors of crystal growth through structural mimicry suggests a novel approach to preventing and treating crystal diseases.
KeywordsKidney stones Cystinuria l-cystine Atomic force microscopy Molecular imposter l-cystine dimethylester l-cystine methylester
This work was supported in part by a pilot project grant (no. 434056) from the Rare Kidney Stone Consortium (U54KD083908), which is a part of the NIH Rare Diseases Clinical Research Network, supported through collaboration between the NIH Office of Rare Diseases Research at the National Center for Advancing Translational Sciences and National Institute of Diabetes and Digestive and Kidney Disease.
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Conflict of Interest
Michael H. Lee declares no conflict of interest. Amrik Sahota declares the following: co-author of patent application, US patent application number 14/146,103; consultant, Omnia Diagnostics, North Brunswick, NJ. Michael D. Ward declares the following: Holder of patent US 20120316236 A1 David S. Goldfarb declares that he is a consultant to Astra Zeneca and Retrophin and owner of Ravine Group.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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