Anti-Atherogenic Effects Shown in Phase I Trial of Receptor Antagonist
April 9, 2010 – A preclinical study shows the action of a toll-like receptor (TLR) antagonist helps reduce atherosclerosis in mice. The data on new antagonists TLR7 and TLR9 on the anti-atherogenic effects in ApoE-/- mouse model of atherosclerosis was made at the American Heart Association conference Arteriosclerosis, Thrombosis and Vascular Biology 2010 Scientific Sessions, April 8-10 in San Francisco.
“We evaluated our TLR antagonist candidates in preclinical models of atherosclerosis to elucidate the mechanism by which they reduce key risk factors associated with atherosclerosis,” said Tim Sullivan, Ph.D., vice president of development programs and alliance management, Idera Pharmaceuticals. “The data presented today show that treatment with a TLR antagonist resulted in increased serum concentrations of IL-10 and that there was an inverse correlation between reduction of total cholesterol and increased serum IL-10,”
A dual TLR7 and TLR9 antagonist candidate was evaluated in a high-fat diet mouse model of atherosclerosis. ApoE-/- mice fed a high-fat diet showed increased body weight gain and higher serum levels of total cholesterol, low-density lipoprotein cholesterol, free fatty acids, bilirubin and leptin as compared to mice fed a normal diet. Treatment of mice fed a high-fat diet with a dual antagonist of TLR7 and TLR9 resulted in control of body weight gain. Mice given the TLR antagonist also showed reductions in total cholesterol, low-density lipoprotein cholesterol, hepatic and kidney steatosis, and plaque formation. TLR antagonist treated mice showed increased serum concentrations of adipokine and interleukin-10 (IL-10), and there was an inverse correlation between total cholesterol and IL-10.
IL-10 is an anti-inflammatory cytokine that regulates many aspects of immune system activity and has been shown to have anti-atherogenic properties in preclinical models.
Idera is conducting a phase 1 clinical trial of IMO-3100, a lead antagonist of TLR7 and TLR9 intended for application in autoimmune and inflammatory diseases.
For more information: www.iderapharma.com
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