A drug currently used to treat rheumatoid arthritis could be used to treat people with a genetic kidney disease reports a study published online this week 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.
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