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Regulus Therapeutics finds microRNA link in tumour growth

Cambridge, MassachusettsTuesday, November 11, 2008, 08:00 Hrs  [IST]

Regulus Therapeutics LLC, a joint venture between Alnylam Pharmaceuticals, Inc. and Isis Pharmaceuticals, Inc. formed to discover, develop, and commercialize microRNA-based therapeutics, announced the publication of new research findings in the journal Cancer Cell pathways in cancer, specifically in malignant brain tumours. Angiogenesis is a physiological process required for the growth and spread of many cancers and the new findings demonstrated that miR-296 is a significant regulator of this pathway. Further, targeting miR-296 with anti-miR-296 antisense oligonucleotides (also called "antagomirs") blocked angiogenesis in tumour xenograft models in mice. This new research was led by Thomas Würdinger affiliated with Xandra O. Breakefield's laboratory at Massachusetts General Hospital and VU Medical Center in Amsterdam, working in collaboration with researchers from Regulus, Anna M. Krichevsky's laboratory at Brigham and Women's Hospital, and Ludwig-Maximilians-University in Munich. "This new research adds to a rapidly growing body of evidence suggesting that microRNAs control important biological pathways and that inhibiting the function of a single microRNA could have a profound effect on disease pathophysiology," said Peter Linsley, Ph.D., Chief Scientific Officer of Regulus Therapeutics. "The current study shows that miR-296 is a significant regulator of tumour induced angiogenesis, and that anti-miR-296 may thus represent a novel anti-cancer strategy." The new paper (Würdinger et al., Cancer Cell 14, 382-393) describes the role of endothelial cell-expressed miR-296 in regulating the formation of new blood vessels. During neovascularization, increased expression of miR-296 represses hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), which in turn regulates additional growth factor receptors, VEGFR and PDGFR. By inhibiting miR-296 with an anti-miR, levels of the growth factor receptors were decreased resulting in decreased growth of blood vessels. The induction of miR-296 expression was observed in tumour blood vessels isolated from human glioblastoma tumors, suggesting an important role for miR-296 in tumour progression and metastatic potential. The data showed that the regulation of miR-296 in human endothelial cells directly resulted in the modulation of angiogenesis in vitro. Additionally, the specific inhibition of miR-296 in an in vivo tumour xenograft model resulted in decreased neovascularization of tumours. microRNAs are a recently discovered class of genetically encoded small RNAs, approximately 20 nucleotides in length, and are believed to regulate the expression of a large number of human genes. microRNA-based therapeutics represent a new approach for the treatment of a wide range of human diseases. The inappropriate absence or presence of specific microRNAs in various cells has been shown to be associated with specific human diseases including cancer, viral infection, metabolic disorders and inflammatory disease. Targeting microRNAs with novel therapeutic agents could result in novel and broadly acting treatments for human diseases. Regulus Therapeutics LLC is a biopharmaceutical company formed to discover, develop, and commercialize microRNA-based therapeutics. Regulus aspires to translate one of the most important new discoveries in biology into a novel new approach for innovative medicine and to build the leading microRNA company.

 
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