title: PEGylated derivatives of cystamine as enhanced treatments for nephropathic cystinosis.
abstract: The genetic disease, nephropathic cystinosis is characterized by lysosomal accumulation of the amino acid cystine. Crystallization of cystine in affected organs, if untreated, results in mortality of the affected individuals by their middle to late teens. The only approved treatment for cystinosis is administration of cysteamine. However, cysteamine is associated with an offending odor and taste and this, coupled to a rapid first pass metabolism and a 6h dosing regimen, suggest a clear need to improve the therapy. A number of PEGylated derivatives of cystamine, the disulfide counterpart of cysteamine, have been synthesised and evaluated in cultured cystinotic fibroblasts for toxicity and efficacy. All of the tested compounds were non-cytotoxic and displayed a remarkable depletion of intralysosomal cystine.
authors.affiliation: School of Pharmacy and Life Sciences, Robert Gordon University, Aberdeen AB10 1FR, UK. z.omran@rgu.ac.uk
authors.forename: Ziad
authors.initials: Z
authors.lastname: Omran
authors.forename: Graeme
authors.initials: G
authors.lastname: Kay
authors.forename: Alberto
authors.initials: A
authors.lastname: Di Salvo
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Knott
authors.forename: Donald
authors.initials: D
authors.lastname: Cairns
mesh_terms: D002478:Cells, Cultured; D003538:Cystamine / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D003554:Cystinosis; D005198:Fanconi Syndrome; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D009404:Nephrotic Syndrome / Q000188:drug therapy; D011092:Polyethylene Glycols / Q000737:chemistry*; D011355:Prodrugs / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity
chemical_list: D011355:Prodrugs; D011092:Polyethylene Glycols; D003538:Cystamine