Advertise With UsAdvertise on our extensive network of industry websites and newsletters.
Get the PBR newsletterSign up to our free email to get all the latest PBR
news.Idera Pharmaceuticals, a clinical-stage biopharmaceutical company developing nucleic acid therapeutics for patients with cancer and rare diseases, has announced the publication of promising preclinical data demonstrating the application of the Company’s novel Gene Silencing Oligonucleotides (GSOs) to inhibit microRNAs implicated in neovascularization, a process that involves the proliferation of blood vessels in tissue and is crucial for recovery following cardiovascular events.
Subscribe to our email newsletter
The studies were conducted by Professor Paul Quax, Ph.D., and Yaël Nossent, Ph.D., of the Department of Surgery, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center in the Netherlands in collaboration with Idera.
The paper, entitled Inhibition of 14q32 microRNAs miR-329, miR-487b, miR-494 and miR-495 Increases Neovascularization and Blood Flow Recovery after Ischemia, appears in the current online edition of Circulation Research.
In this paper, Drs. Quax and Nossent and colleagues report on the identification of specific microRNAs that regulate genes in the pathway involved in neovascularization, including the 14q32 microRNA gene cluster. Idera’s proprietary GSO technology enabled inhibition of these specific microRNAs in both cell-based assays as well as in animal models.
Treatment with GSOs led to microRNA-specific down-regulation and hence up-regulation of the microRNA’s target genes. In a mouse model of double femoral artery ligation, treatment with specific GSOs targeting the identified microRNAs led to improved blood flow recovery after ischemia, increased perfusion and full recovery of tissue perfusion. These data show that GSOs targeting specific microRNAs have therapeutic potential for neovascularization.
"In this important study, we identified a large cluster of microRNAs that is involved in the recovery of blood flow following cardiovascular events," said Dr. Nossent.
"Through our collaboration with Idera and our application of its GSOs, we were able to selectively target each of these microRNAs, elucidating their role in neovascularization. We were also able to demonstrate that inhibition of these specific microRNAs led to accelerated recovery of blood flow, thereby providing a rationale for a novel therapeutic approach."
"GSOs are novel structures designed to overcome the limitations of the currently practiced antisense technology, with a goal of providing an increased therapeutic index," said Walter Strapps, Ph.D., Executive Director of RNA Therapeutics for Idera.
"We are very pleased with the results of our collaboration with Drs. Quax and Nossent, and that we were able to identify GSOs to inhibit specific microRNAs following systemic delivery. We are very encouraged with the emerging data, both internally and externally, supporting the potential of GSOs as third generation antisense therapeutic agents able to overcome the hurdles of current technologies. We are continuing to advance our GSO platform and remain on track to initiate proof-of-concept studies with GSO drug candidates in two disease indications as early as the second half of next year."
Authors of the paper are Sabine M.J. Welten, Msc, Antonius J.N.M. Bastiaansen, MD, Rob C.M. de Jong, Msc, Margreet R. de Vries, PhD, Erna A.B. Peters, Bsc, Martin C. Boonstra, Msc, Paul H.A. Quax, PhD and A. Yaël Nossent, PhD of Leiden University Medical Center; Søren P. Sheikh, MD, PhD of Odense University Hospital; Nicola La Monica, PhD and Ekambar R. Kandimalla, PhD of Idera Pharmaceuticals.