Idera Pharmaceuticals, Inc. (Nasdaq: IDRA) today announced the presentation of preclinical data indicating that its dual antagonist of Toll-like receptor (TLR) 7 and TLR9 reduced restenosis and atherosclerosis in a mouse model of hypercholesterolemia. The studies were conducted in collaboration with Professor Paul Quax, Ph.D., from the Department of Surgery, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, the Netherlands. The oral presentation, entitled “TLR7/9 activation enhances neointima formation in hypercholesterolemic APOE*3Leiden mice,” was made at the American Heart Association (AHA) Scientific Sessions 2011 held in Orlando, FL.
“There is a growing body of evidence that inflammation plays a significant role in cardiac diseases and antagonism of TLRs may interrupt these inflammatory processes,” commented Professor Quax. “By inhibiting TLR7 and TLR9, we were able to reduce inflammation and limit vascular remodeling in a preclinical model. These new preclinical data offer promising in vivo results pointing to a potential therapeutic benefit of TLR7 and TLR9 antagonists in restenosis and accelerated atherosclerosis.”
“In addition to evaluating antagonists of TLR7 and TLR9 in autoimmune diseases, we have been conducting studies of these candidates in preclinical models of cardiovascular diseases. This presentation expands upon our prior studies, in which our TLR7 and TLR9 antagonist candidates suppressed total cholesterol in hyperlipidemic mice, as presented at AHA 2010,” said Nicola La Monica, Vice President of Biology at Idera Pharmaceuticals. “Idera’s TLR7 and TLR9 antagonist candidates have been created through a chemistry-based approach and our lead candidate, IMO-3100, is in clinical development for autoimmune diseases.”
In the present study, TLR7 and TLR9 expression was detected in femoral arteries after surgical intervention, suggesting activation by cellular stress. Formation of neointima after femoral artery cuff placement in hypercholesterolemic APOE*3Leiden mice also was observed. Neointima is a new, thickened inner layer of veins or arteries, commonly formed in patients with atherosclerosis and restenosis after balloon angioplasty. Administration of Idera’s TLR7 and TLR9 dual antagonist led to significant reduction in the formation of neointima, in signs of inflammation, and in induction of IL-10 expression.