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Regulus Therapeutics Presents New Pre-clinical Data on microRNA Therapeutics for Diabetes
Targeting microRNA improves insulin resistance and glucose tolerance in mouse models of diabetes
Carlsbad, CA., April 15, 2010 – Regulus Therapeutics Inc. today announced that new data from its metabolic disease program were presented at the “Diabetes” Keystone Symposium held April 12-17 in Whistler, British Columbia. The new pre-clinical research findings showed that therapeutic oligonucleotides targeting microRNA are able to improve insulin resistance and normalize plasma glucose in mouse models of diabetes while having no significant effect on glucose or insulin levels in normal mice. The increased incidence of diabetes is a growing threat to global health, and microRNA therapeutics represent a promising strategy for the discovery and development of novel anti-diabetic agents.
“Diabetes is a multi-factoral disease that results in disruption of the metabolic system. microRNA therapies that can modulate pathways of disease rather than single molecular targets represent a novel approach for diabetes,” said Peter S. Linsley, Ph.D., Chief Scientific Officer of Regulus. “Further, the ability to deliver anti-miRs to multiple tissues involved in metabolic disease, such as adipose and liver, offers promising opportunities for our therapeutic platform.”
In a presentation entitled “Inhibition of Let-7 with anti-miR oligonucleotides improves insulin resistance in DIO mice,” Regulus scientists described the therapeutic targeting in a mouse model of diabetes of the Let-7 family of microRNAs, which are highly expressed in the liver and adipose, or fat, tissues. Results showed:
· In vivo targeting of members of Let-7 with anti-miRs improved insulin resistance in a diet-induced obesity mouse model;
· Anti-miR inhibition of members of Let-7 in normal mice increased lean mass without affecting blood glucose; and,
· Let-7 messenger RNA target de-repression was verified in both liver and adipose, establishing effective delivery of anti-miRs to these cell types and tissues.
In another presentation entitled “microRNA Networks,” Dr. Markus Stoffel, a Regulus collaborator and member of the Scientific Advisory Board, highlighted microRNA involvement in the biological pathways of metabolic disease.
“The ability to regulate metabolic processes is indispensible for all living cells and the mechanisms of metabolic control are complex involving multiple layers of genetic regulation,” said Markus Stoffel, M.D., Ph.D., Professor at the Swiss Federal Institute of Technology. “microRNAs define a novel class of drug targets that regulate and fine-tune metabolic pathways. Accordingly, microRNA therapeutics hold significant promise as a new modality for the treatment of diabetes and metabolic diseases more broadly.”
“We believe an advantage of developing microRNA-based medicines for diabetes and metabolism is the relatively quick path to clinical proof-of-concept in humans. Glucose and insulin levels are objective and well-accepted endpoints which can be readily measured following brief treatment durations to demonstrate clinical efficacy,” said Hubert C. Chen, M.D., Vice President of Translational Medicine of Regulus. “microRNA targets for metabolism such as Let-7, along with our anti-miR-122 program in hepatitis C infection, will give us multiple opportunities to clinically validate microRNA biology in humans.”
About microRNAs
The discovery of microRNA in humans is one of the most exciting scientific breakthroughs in the last decade. microRNAs are small RNA molecules, typically 20 to 25 nucleotides in length, that do not encode proteins but instead regulate gene expression. Nearly 700 microRNAs have been identified in the human genome, and more than one-third of all human genes are believed to be regulated by microRNAs. As a single microRNA can regulate entire networks of genes, these new molecules are considered the master regulators of the genome. microRNAs have been shown to play an integral role in numerous biological processes including the immune response, cell-cycle control, metabolism, viral replication, stem cell differentiation and human development. Most microRNAs are conserved across multiple species indicating the evolutionary importance of these molecules as modulators of critical biological pathways. Indeed, microRNA expression or function has been shown to be significantly altered in many disease states, including cancer, heart failure and viral infections. Targeting microRNAs with anti-miRs, antisense oligonucleotide inhibitors of microRNAs, or miR-mimics, double-stranded oligonucleotides to replace microRNA function, opens the possibility of a novel class of therapeutics and a unique approach to treating disease by modulating entire biological pathways. To learn more about microRNAs please visit http://www.regulusrx.com/microrna/microrna-explained.php
About Regulus Therapeutics Inc.
Regulus Therapeutics is a biopharmaceutical company leading the discovery and development of innovative new medicines based on microRNAs. Regulus is targeting microRNAs as a new class of therapeutics by working with a broad network of academic collaborators and leveraging oligonucleotide drug discovery and development expertise from its founding companies Alnylam Pharmaceuticals (Nasdaq:ALNY) and Isis Pharmaceuticals (Nasdaq:ISIS). Regulus is advancing microRNA therapeutics towards the clinic in several areas including hepatitis C infection, cardiovascular disease, fibrosis, oncology, immuno-inflammatory diseases, and metabolic diseases. Regulus’ intellectual property estate contains both the fundamental and core patents in the field as well as over 600 patents and more than 300 pending patent applications pertaining primarily to chemical modifications of oligonucleotides targeting microRNAs for therapeutic applications. In 2008, Regulus entered into a major alliance with GlaxoSmithKline to discover and develop microRNA therapeutics for immuno-inflammatory diseases. In 2010, Regulus entered into a new collaboration with GlaxoSmithKline to develop and commercialize microRNA therapeutics targeting microRNA-122 for the treatment of Hepatitis C Viral infection. For more information, visit www.regulusrx.com.
Forward-Looking Statements
This press release includes forward-looking statements regarding the future therapeutic and commercial potential of Isis’, Alnylam’s and Regulus’ business plans, technologies and intellectual property related to microRNA therapeutics being discovered and developed by Regulus, including statements regarding the therapeutic potential of targeting Let-7 and miR-122. Any statement describing Isis’, Alnylam’s or Regulus’ goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such products. Such parties’ forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause their results to differ materially from those expressed or implied by such forward-looking statements. Although these forward-looking statements reflect the good faith judgment of the management of each such party, these statements are based only on facts and factors currently known by Isis, Alnylam or Regulus, as the case may be. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Regulus’, Alnylam’s, and Isis’ programs are described in additional detail in Alnylam’s and Isis’ annual reports on Form 10-K for the year ended December 31, 2009. Copies of these and other documents are available from Alnylam or Isis.
