Isis Pharmaceuticals, Inc. announced the results from multiple preclinical studies demonstrating potent and selective antisense inhibition of multiple gene targets involved in metabolic disorders including type 2 diabetes.
Antisense drugs are very specific, making them an ideal approach for the inhibition of individual members of complex gene families and for evaluating the role of these individual genes in metabolic diseases. Due to their specificity, antisense drugs can target individual phosphatases, kinases and transcription factors, several of which are difficult to inhibit selectively with small molecules. Findings from the studies were presented by Isis and collaborators during the American Diabetes Association's (ADA) 66th Scientific Sessions in Washington, DC.
"The efficiency of Isis' antisense drug discovery programme allows us to rapidly validate novel targets in vivo for a broad range of complex diseases, including metabolic disorders," said C. Frank Bennett, Ph.D., Senior Vice President, Research at Isis Pharmaceuticals. "In our metabolics program at Isis, we have examined over 100 targets. Because of the selectivity of our drugs, we are able to observe the unique role that inhibition of one gene target plays compared to another. By comparing inhibition of these targets, we have selected the best ones to move forward, including our PTP-1B inhibitor, ISIS 113715, which is in Phase 2 clinical trials. Inhibition of several of these targets has resulted in beneficial effects that extend far beyond glucose control and include reduction of hyperlipidemia and body weight, both problems that are commonly seen in type 2 diabetes patients. As the data we presented today show, we have a robust pipeline of preclinical leads following behind this exciting drug."
Dr. Gerald Shulman, M.D., Ph.D., Professor of Internal Medicine and Cellular and Molecular Physiology, Yale University School of Medicine, has been a close collaborator of Isis for the past 2 years investigating the role of multiple gene targets in animal models for diabetes, obesity and fatty liver disease. Dr. Shulman said, "We have evaluated over a dozen of Isis' second-generation antisense drugs and we were very encouraged to see that antisense inhibition of PKC-epsilon in animal models of diabetes prevented the development of fatty liver and fat induced insulin resistance. The pharmacological activity demonstrated with the PKC-epsilon antisense drug has great therapeutic potential for the treatment of type 2 diabetes and non alcoholic liver disease."