Idera Pharmaceuticals, Inc. (Nasdaq: IDRA) presented data on the
evaluation of a Toll-like receptor (TLR) antagonist in a preclinical
hyperlipidemia model today at the Keystone Symposia conference “Advances
in Molecular Mechanisms of Atherosclerosis” being held in Banff,
Alberta, Canada. Idera’s proprietary TLR antagonists have dual activity
for both TLR7 and TLR9, and present a potentially innovative 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” (abstract #208), was
made by Idera scientists. In the studies presented, a dual antagonist of
TLR7 and TLR9 was evaluated in mice fed a high-fat diet to induce
hyperlipidemia. Treatment with the antagonist resulted in reduced serum
total cholesterol, LDL-cholesterol, leptin, hepatic and kidney
steatosis, and body weight gain compared to control mice on high-fat
diet.
“Control of atherogenic lipids by a novel antagonist of TLR7
and 9 in mouse models of hyperlipidemic disease”
“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,” said Tim Sullivan, Ph.D.,
Vice President of Development Programs. “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.”
In the studies presented today, 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. 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 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 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 initiation of a Phase 1 clinical trial of
IMO-3100, a lead TLR7/9 antagonist for intended application in
autoimmune and inflammatory diseases.
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