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Renal disease

Renal disease

Angiopoietin-like 4 (ANGPTL4);
integrin aVb5

Rat studies suggest ANGPTL4 variants that selectively bind to integrin aVb5 could help prevent proteinuria in nephrotic syndrome. Proteinuria and hypertriglyceridemia are hallmarks of nephrotic syndrome but have not been functionally linked. In rat models of a precursor phase of nephrotic syndrome, Angptl4 overexpression in adipose tissue increased plasma levels of Angptl4, which decreased proteinuria but also increased hypertriglyceridemia, compared with normal Angptl4 expression. In the same models, a recombinant, mutant form of ANGPTL4 that did not interact with lipoprotein lipase (Lpl) but retained its interaction with aVb5 on renal cells decreased proteinuria compared with wild-type ANGPTL4 without raising triglyceride levels. Ongoing studies include pharmacokinetic studies of ANGPTL4 mutants and scaling up production of the proteins for preclinical toxicity studies.

SciBX 7(4); doi:10.1038/scibx.2014.123
Published online Jan. 30, 2014

Patent application filed covering use of ANGPTL4 mutants in proteinuric disorders; available for licensing from the UAB Research Foundation
Deborah J. Bidanset-Ponder,
UAB Research Foundation, Birmingham, Ala.

Clement, L.C. et al. Nat. Med.; published online Dec. 8, 2013;
Contact: Sumant S. Chugh, The University of Alabama at Birmingham, Birmingham, Ala.