New preclinical data from Regulus' miR-21 study on kidney fibrosis

Regulus Therapeutics Inc., a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs, today announced that new preclinical data investigating the role of microRNA-21 (miR-21) in the treatment of kidney fibrosis has been published in the journal Science Translational Medicine. Regulus' lead program for fibrosis targets miR-21, which is up-regulated in fibrotic tissues of humans. Previous preclinical studies by Regulus scientists and collaborators have shown that therapeutic oligonucleotides targeting miR-21 (anti-miR-21) can decrease fibrosis in preclinical models by reducing the expression of extracellular matrix proteins. Despite the current burden of fibrosis-related human disease, there are few therapies that can specifically treat this devastating disease.

"We are pleased with the published results demonstrating that targeting miR-21 with proprietary anti-miR oligonucleotides is effective at preventing kidney fibrosis in preclinical models," said Neil W. Gibson, Ph.D., Regulus' Chief Scientific Officer. "We plan to select an anti-miR-21 development candidate this year for advancement into the clinic in the near future and are excited about the potential to bring this innovative treatment to patients with fibrotic diseases."

"Expression of miR-21 was found to be increased in fibrotic kidney samples from animal models and human patient samples. Genetic deletion of miR-21 in preclinical models protected kidneys from fibrosis and treatment with anti-miRs targeting miR-21 also blocked fibrosis in preclinical models," said Dr. Duffield, M.D., Ph.D. Associate Professor of Medicine, in the Division of Nephrology, at the University of Washington. "Taken together, these data suggest that anti-miR-21 could have a therapeutic benefit in patients with chronic kidney disease."

In the published study, Regulus and its collaborators from the University of Washington investigated the role of miR-21 in kidney fibrosis. Genetic deletion of miR-21 in mice resulted in no overt abnormality, however, these miR-21 knock out mice suffered less fibrosis in response to kidney injury, which was pheno-copied in wild-type mice treated with anti-miR-21 oligonucleotides. Analysis of gene expression profiles identified groups of genes involved in metabolic pathways that were up-regulated in the absence of miR-21, in particular genes involved in lipid metabolism and enhanced oxygen radical production. Systemic administration of anti-miR-21 effectively reversed the deleterious effects of miR-21 in kidney injuries. These animal studies demonstrate that miR-21 contributes to fibrogenesis and epithelial injury in the kidney in two mouse models and is a candidate target for anti-fibrotic therapies.