Anti-IL-4Rα aptamer reduces IL-4 signaling and formation of nasal polyps

• Published in: ERJ open research p. 700
• Main Authors: Saheb Sharif-Askari, Fatemeh, Hafezi, Shirin, Hachim, Ibrahim, Mdkhana, Bushra, Khalid, Baraa, Al-Sheakly, Salah, Saheb Sharif-Askari, Narjes, Selvakumar, Balachandar, Halwani, Rabih
• Format: Journal Article
• Language: English
• Published: 14-11-2024
• ISSN: 2312-0541; 2312-0541
• DOI: 10.1183/23120541.00700-2024

Aptamers are RNA- or DNA-based oligomers with high protein-specific binding properties that have demonstrated effectiveness in targeting various proteins and treating diseases such as cancer. However, their application in regulating chronic respiratory diseases, such as chronic rhinosinusitis, is not well established. Therefore, in this study, we used the anti-IL-4Rα aptamer (anti-IL-4Rα apt) to investigate its impact on IL-4R signaling and related Th2-type inflammation in nasal polyp tissue. To achieve this, we treated nasal polyp tissue extracted from chronic rhinosinusitis with nasal polyps (CRSwNP) patients who had undergone polypectomy with the anti-IL-4Rα apt. Interestingly, we observed that the treatment resulted in a significant reduction in IL-4-STAT6 signaling and Th2-mediated inflammation, as demonstrated by an approximately 2-fold decrease in the levels of IL-4Rα, phosphorylated STAT6 (p-STAT6), and GATA3 in treated nasal polyp (NP) tissues compared to the untreated uncinate process (p<0.001). Additionally, to evaluate the effects of the anti-IL-4Rα apt on nasal polyp formation, we first established an eosinophilic mouse model of CRSwNP, aiming to mimic the Th2 inflammatory pathogenesis observed in CRSwNP. Notably, we observed that the administration of the anti-IL-4Rα apt effectively reduced nasal polyp formation and Th2-mediated inflammation, as shown by an approximately 3-fold reduction in the percentages of IL-4Rα, GATA3, and p-STAT6 positive cells in the nasal tissues of this mouse model (p<0.001). Given that the anti-IL-4Rα aptamer demonstrated comparable efficacy to dupilumab-an anti-IL-4Rα therapy proven effective for CRSwNP, this research highlights the potential therapeutic efficacy of aptamers in managing chronic inflammatory conditions such as those seen in CRSwNP.