Cystinuria: Genetic Aspects and Novel Pharmacotherapeutics

Abstract

This review provides an overview of the genetic aspects of cystinuria, as well as the novel pharmacotherapeutics that could potentially be used to treat the disease. Cystinuria is an inherited disorder characterized by the formation of painful stones in the kidneys, bladder, and other parts of the renal system. Currently, mutations responsible for cystinuria have been identified in two genes (SLC3A1 and SLC7A9 ), and cystinuria patients are categorized based on their genotypes - which versions, or alleles, of these genes they have (mutated or wild-type). Regardless of genotype, however, current treatments for all cystinuria patients have significant limitations. This has led researchers to search for more promising therapeutics. One potential treatment uses cystine analogs—compounds that are structurally similar to cystine, which is the naturally occurring chemical substance from which the stones are formed. These compounds have demonstrated the ability to inhibit stone formation by stunting cystine crystallization – the process by which cystine crystals aggregate to form stones. Gene therapy may also be used to treat cystinuria in the future by replacing mutated copies of SLC3A1 and SLC7A9 with healthy ones. Technological advancements and an improvement of our understanding of how gene therapy functions in the renal system could reveal even more treatment possibilities.