Abstract Number: PB2006
Meeting: ISTH 2020 Congress
Background: The Apta-1 aptamer is an RNA oligonucleotide sequence selected to bind with high affinity and selectivity to a specific functional molecular motif. Since Apta-1 binding sequence is present on different proteins, Apta-1 displays multiple effects in various animal models. This unique feature makes Apta-1 a suitable candidate for treatment of complex pathophysiological conditions, such as Systemic Inflammatory Response Syndrome (SIRS) or sepsis.
Aims: The effects of Apta-1 on severe systemic inflammation were investigated in vivo in non-human primate animal model.
Methods: The 15 mg/kg of LPS endotoxin (strain K-235) was administered intravenously to all Cynomolgus monkeys. Apta-1 treated animals received Apta-1 intravenously in two doses, 20 mg/kg at 15 min and 10 mg/kg at 120 minutes post LPS infusion. Untreated animals received saline solution at the same time points. Plasma and serum samples were collected from all animals at 3, 6, 12, 24 and 48 hours after LPS infusion. Selected markers of vascular damage, inflammation and coagulation were analyzed.
Results: Markers of vascular damage, i.e. myoglobin, metalloprotease 9 and damage associated endogenous patterns (S1008/MRP8 and HMGB1) were induced in blood samples after LPS infusion. Animals treated with Apta-1 showed decreased levels of pro-inflammatory markers, i.e. IL-6, IL-1beta, TNF-alpha and serum amyloid A (SAA); as well as complement fragments C3a and C4a. Furthermore, anti-inflammatory cytokine IL-10 levels were 2-fold increased. Administration of Apta-1 also resulted in prolonged blood coagulation (aPTT). Most importantly, Apta-1 induced plasma levels of Pentraxin 3 (PTX3) up to 5- fold. Pentraxin 3 is a known complement modulator.
Conclusions: In this study, treatment with the novel RNA aptamer Apta-1resulted in suppression of inflammation, prolongation of coagulation and induction of tissue repair mediated via upregulation of Pentraxin 3. The multifactorial activity of Apta-1 affects different components of dysregulated immune response, thus restoring its protective function.
To cite this abstract in AMA style:Jedlina L, Casslén V, Chutná Olin O, Bylock A, Lindstam M. Promising Therapeutic Effects of a Novel RNA Aptamer, Apta-1, in a Severe Systemic Inflammation Model on Non-human Primates [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/promising-therapeutic-effects-of-a-novel-rna-aptamer-apta-1-in-a-severe-systemic-inflammation-model-on-non-human-primates/. Accessed September 29, 2023.
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