-New study published in Science Translational Medicine demonstrates microRNA-21 contributes to fibrogenesis in the kidney
-Regulus, in partnership with Sanofi, developing novel anti-fibrotic therapies targeting microRNAs
B.N. Chau et al.
“MicroRNA-21 Promotes Fibrosis of the Kidney by Silencing Metabolic Pathways”
Sci Transl Med 15 February 2012:
Vol. 4, Issue 121, p. 121ra18
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3003205
LA JOLLA, Calif., Feb. 16, 2012 /PRNewswire/ — 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 [click to continue…]
-Regulus Scientists to Provide Update on Lead Therapeutic Program at American Society of Nephrology Meeting-
LA JOLLA, Calif., Nov. 8, 2011 /PRNewswire/ — Regulus Therapeutics Inc., a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs, today announced presentations on its preclinical programs for the treatment of fibrosis at the American Association of Nephrology “Kidney Week” Annual Meeting held Nov. 8–13, 2011, in Philadelphia. New data will be presented demonstrating that microRNA-21 (miR-21) is upregulated in human patients and animal models with kidney injury and fibrosis. In preclinical models, genetic deletion of miR-21 or pharmacologic inhibition using proprietary anti-miR oligonucleotides decreased fibrotic gene expression and improved kidney fibrosis. These new data demonstrate that miR-21 contributes to fibrosis and epithelial injury in the kidney, and supports the development of anti-miR-21 oligonucleotides as a therapeutic approach for treating chronic kidney disease.
“In collaboration with Dr. Jeremy S. Duffield, M.D., Ph.D., University of Washington, we have shown that inhibition of miR-21 with our proprietary anti-miR oligonucleotides is effective at preventing [click to continue…]
Bone morphogenetic proteins (BMPs) play essential roles in the control of skin development, postnatal tissue remodelling and tumorigenesis. To explore whether some of the effects of BMP signalling are mediated by microRNAs, Natalia V. Botchkareva’s lab at the Centre for Skin Sciences (University of Bradford, Yorkshire, UK), performed genome-wide microRNA (miRNA) screening in primary mouse keratinocytes after BMP4 treatment. Microarray analysis revealed substantial BMP4-dependent changes in the expression of distinct miRNAs, including miR-21. Real-time PCR confirmed that BMP4 dramatically inhibits miR-21 expression in the keratinocytes. Consistently, significantly increased levels of miR-21 were observed in transgenic mice overexpressing the BMP antagonist noggin under control of the K14 promoter (K14-noggin). By in situ hybridization, miR-21 expression was observed in the epidermis and hair follicle epithelium in normal mouse skin. In K14-noggin skin, miR-21 was [click to continue…]
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microRNA-21 is a very popular study target these days, which is not surprising given its overexpression in many human tumors, and was profiled on the miRNA blog back in February as the “microRNA of the week”.
Researchers at Yale have now demonstrated what they call ‘oncomiR addiction’ (the dependence of some cancer types on certain microRNAs for maintenance of the malignant phenotype) for miR-21 by pre-B-cell lymphoma. They show for the first time in vitro that overexpression of miR-21 leads to a pre-B malignant lymphoid-like phenotype and that when miR-21 is inactivated, the tumors regress completely in a few days. Their research not only demonstrates that mir-21 is a genuine oncogene but that tumors can also become addicted to oncomiRs. This and other work supports miR-21 as a drug target for treatment of human cancers.
Medina PP, Nolde M, Slack FJ (2010) OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma. Nature [Epub ahead of print]. [abstract]
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