Anti-IL-17 nucleic acid aptamer alleviates motor impairment in mouse spondyloarthritis model

Abstract

Spondyloarthritis (SpA) is a group of rheumatic disorders characterized by chronic inflammation of the spine, joints, entheses, and other symptoms outside the musculoskeletal system. SpA affects 0.5%-2% of the global population and leads to significantly decreased life quality, increased mortality, and substantial health care-related costs, imposing a high burden not only on patients, but also on society. There is robust experimental and clinical evidence supporting the central role of interleukin (IL)-17A-pathway in inflammation, bone erosion and fusion associated with SpA. Currently, several antibody-based therapeutics selective to IL-17 are now applied in clinical practice. Nevertheless, the search is still ongoing for alternative targeted molecules with lower manufacturing costs, minimal batch-to-batch variations and tolerance to wide range of transportation and storage conditions. Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) aptamers seem to be very promising candidates for targeted therapy, particularly in the context of rheumatic diseases. In this study, we evaluated the effects of anti-IL-17A 2’-F-RNA aptamer Apt3-4 on a mouse model of proteoglycan-induced spondyloarthritis in comparison with a commonly used anti-inflammatory drug, diclofenac. We have shown that the injection of the aptamer alleviates the motor impairment in SpA mice in the motor field test with minimal side effects.