Therapy with 2'-O-Me Phosphorothioate Antisense Oligonucleotides Causes Reversible Proteinuriaby Inhibiting Renal Protein Reabsorption

Precise and reliable tools are essential to quickly assess adverse effects of new drug candidates. Drug induced kidney injury was a difficult to approach issue for a long time. A recent study of BioMarin addresses why their anti-sense oligonucleotide therapeutic causes a reversible proteinuria in animal and clinical studies. By using Cell4Pharma’s ciPTEC cells, an immortalized human kidney epithelial cell line, BioMarin could reveal the mechanisms of toxicity. The oligonucleotide competes with the uptake of proteins in proximal tubular epithelial cells resulting in elevated protein levels in the urine.