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news.Idera Pharmaceuticals (Idera) has presented data on the evaluation of a Toll-like receptor (TLR) antagonist in a preclinical hyperlipidemia model, at the Keystone Symposia conference, 'Advances in Molecular Mechanisms of Atherosclerosis' being held in Banff, Alberta, Canada.
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Idera’s proprietary TLR antagonists have dual activity for both TLR7 and TLR9, and is said to present a potentially new approach for the treatment of certain autoimmune diseases.
The presentation, entitled ‘Control of atherogenic lipids by a novel antagonist of TLR7 and 9 in mouse models of hyperlipidemic disease’, was made by Idera scientists. In the studies presented, a dual antagonist of TLR7 and TLR9 was evaluated in mice who was fed a high-fat diet to induce hyperlipidemia.
In the studies, a TLR antagonist candidate was evaluated in a high-fat diet mouse model of hyperlipidemia. Mice fed a high-fat diet had elevated total serum cholesterol (T-C) and low-density lipoprotein cholesterol (LDL-C), elevated serum leptin, increased hepatic and renal steatosis, and increased body weight gain relative to mice fed a normal diet.
The treatment with an antagonist of TLR7 and TLR9 showed dose-dependent reduction of the high-fat diet effects on T-C, LDL-C, leptin, steatosis, and body weight gain, as compared to control mice fed a high-fat diet. Treatment of mice fed a high-fat diet with the TLR antagonist had no effect on serum levels of high-density lipoprotein cholesterol (HDL-C).
The companies said that the studies were conducted with a strain of mice that were deficient in apolipoprotein E (ApoE-/-) and also with a strain of mice with normal lipid metabolism (C57BL/6).
Idera recently announced the initiation of a phase 1 clinical trial of IMO-3100, a lead TLR7/9 antagonist for intended application in autoimmune and inflammatory diseases.
Tim Sullivan, vice president of development programs at Idera, said: “We are developing our TLR antagonists for potential treatment of autoimmune diseases and have shown potent activity in preclinical models of lupus, rheumatoid arthritis and psoriasis.
“There is evidence that patients with these autoimmune diseases have increased incidence of hyperlipidemia and other cardiovascular risk factors. The preclinical results suggest our TLR antagonists may address both hyperlipidemia and the underlying autoimmune disease in these patients.”