Vladimir Koval

Background/Objectives: Interleukin-17A (IL-17A) is a key pathogenic cytokine in autoimmune arthropathies. Current monoclonal antibody inhibitors targeting the IL-17/IL-17RA axis demonstrate clinical efficacy but face significant limitations, including immunogenicity, the loss of therapeutic response, and cold-chain storage. Our study evaluated oligonucleotide aptamers targeting IL-17A and its receptor as an alternative to monoclonal antibodies to suppress an IL-17A-induced inflammatory response in cell models relevant to immunoinflammatory rheumatic diseases. Methods: We examined three aptamers: 2′-F-RNA aptamers Apt21-2 and Apt3-4 specific to IL-17A and DNA aptamer RA10-6 targeting the receptor of IL-17A. Their ability to suppress IL-17A functional activity was assessed in peripheral blood mononuclear cells (PBMCs) from healthy donors and personalized fibroblast-like synoviocytes (FLSs) from patients with axial spondyloarthritis (axSpA) and rheumatoid arthritis (RA). Inhibition was measured by quantifying IL-6 and MMP-13 secretion using ELISA and flow cytometry, using secukinumab as a reference control. Results: In PBMC, all aptamers suppressed IL-17A-stimulated IL-6 secretion and cell proliferation in a concentration-dependent manner (17–200 nM), with a 65–85% efficacy, comparable to that of secukinumab. In axSpA-derived FLS, we observed time-dependent efficacy: At 4 h, all three aptamers suppressed IL-6 to the same extent as secukinumab; at 24 h, RA10-6 maintained high efficacy while Apt21-2 and Apt3-4 showed reduced activity. A combination of receptor-targeting RA10-6 with anti-IL-17A aptamers resulted in synergistic IL-6 suppression. All aptamers reduced MMP-13 to basal levels. RA-derived FLS showed diminished responses to all inhibitors. Conclusions: Aptamers demonstrate high specificity and sustained efficacy in suppressing IL-17A signaling for an in vitro model of spondyloarthritis, with superior performance over antibodies. Disease-dependent differential efficacy in RA FLS reflects heterogeneity consistent with limited clinical anti-IL-17 efficacy in RA. These findings show the strong potential of the studied aptamers as an alternative to monoclonal antibodies for IL-17-associated inflammatory arthropathies, particularly spondyloarthritis.

Osteoporosis is becoming a “silent pandemic” because of its ever-increasing prevalence and the absence of clinical manifestations until a bone fracture happens. The purpose of this review is to summarize the actual data on the pathogenesis of osteoporosis and its treatment options. The disease develops through a multifactorial process involving an imbalance between bone remodeling and different factors like genetics, non-coding RNA regulation, osteoimmune dysregulation, oxidative stress, cellular senescence, and fat–bone interactions. Existing medications have beneficial effects by preserving and increasing bone density and reducing the risk of fractures. Among them, there are bisphosphonates, strontium ranelate, calcitonin, estrogen-progestin therapy, selective estrogen receptor modulators, and parathyroid hormone analogues. Otherwise, they suffer from certain disadvantages, such as adverse effects, including serious ones, and limitations associated with comorbidity. Targeting pathways underlying bone metabolism could significantly improve the therapeutic options and provide new tools in the fight against osteoporosis. We consider here targeted therapeutics that are already in clinical practice, as well as the most promising novel agents that are now under development: antibodies, siRNAs, aptamers, and small molecules.