Regulus Therapeutics' metabolic disease program data presented at Diabetes Keystone Symposium

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.

“Inhibition of Let-7 with anti-miR oligonucleotides improves insulin resistance in DIO mice”

"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."