News | April 08, 2010

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:

Related Content

ESC 2017 late breaking trial hot line study presentations.
News | Clinical Study| September 12, 2017
September 12, 2017 – The European Society of Cardiology (ESC) Congress 2017 includes several Hot Line Late-breaking C
U.K., NHS studies, weekend effect, hospital admission, atrial fibrillation, heart failure
News | Clinical Study| June 28, 2016
New research shows patients admitted to National Health Service (NHS) hospitals in the United Kingdom for atrial...
stroke risk
News | Clinical Study| August 28, 2015
Most people assume strokes only happen to octogenarians, but recent evidence suggests that survivors of childhood can
Overlay Init