A drug currently used to treat rheumatoid arthritis could be used to treat people with a genetic kidney disease reports a study published online in Nature Medicine.
Autosomal dominant polycystic kidney disease (ADPKD), a condition characterized by the formation of cysts in the kidneys, is caused by mutations in the genes that encode the proteins polycystin-1 and -2. Rong Li and colleagues show that tumour necrosis factor-alpha (TNF-alpha), an inflammatory signalling protein present in the cystic fluid of humans with ADPKD, disrupts the accumulation of polycystin-2 to the cell membrane and primary cilia.
Giving TNF-alpha to mice susceptible to developing cysts, owing a mutation in the gene coding for polycystin-2, resulted in the intensification of disease. By contrast, treatment of the same mice with the TNF-alpha inhibitor etanercept, which is used to treat rheumatoid arthritis, prevented cyst formation.
These data reveal a pathway connecting TNF-alpha, the polycystins and cystogenesis, and suggest that etanercept might be useful to treat people with ADPKD.
Rong Li (Stowers Institute for Medical Research, Kansas City, MO, USA)
Abstract available online.
(C) Nature Medicine press release.
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