Metabolomics

Dataset Information

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Cysteamine-bicalutamide combination therapy corrects proximal tubule phenotype in cystinosis


ABSTRACT: Nephropathic cystinosis is a severe monogenic kidney disorder caused by mutations in CTNS, encoding the lysosomal transporter cystinosin, resulting in lysosomal cystine accumulation. The sole treatment, cysteamine, slows down the disease progression, but does not correct the established renal proximal tubulopathy. Here, we developed a new therapeutic strategy by applying omics to expand our knowledge on the complexity of the disease and prioritize drug targets in cystinosis. We identified alpha-ketoglutarate as a potential metabolite to bridge cystinosin loss to autophagy, apoptosis and kidney proximal tubule impairment in cystinosis. This insight combined with a drug screen revealed a bicalutamide-cysteamine combination treatment as a novel dual-target pharmacological approach for the phenotypical correction of cystinotic kidney proximal tubule cells, patient-derived kidney tubuloids and cystinotic zebrafish.

INSTRUMENT(S): Liquid Chromatography MS - alternating - hilic

SUBMITTER: Esther Zaal 

PROVIDER: MTBLS2538 | MetaboLights | 2021-06-24

REPOSITORIES: MetaboLights

Dataset's files

Source:
Action DRS
MTBLS2538 Other
FILES Other
a_MTBLS2538_LC-MS_alternating_hilic_metabolite_profiling.txt Txt
i_Investigation.txt Txt
m_MTBLS2538_LC-MS_alternating_hilic_metabolite_profiling_v2_maf.tsv Tabular
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Nephropathic cystinosis is a severe monogenic kidney disorder caused by mutations in CTNS, encoding the lysosomal transporter cystinosin, resulting in lysosomal cystine accumulation. The sole treatment, cysteamine, slows down the disease progression, but does not correct the established renal proximal tubulopathy. Here, we developed a new therapeutic strategy by applying omics to expand our knowledge on the complexity of the disease and prioritize drug targets in cystinosis. We identified alpha-  ...[more]

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