OC-17 | Profiling miR-30a expression in patients with episodic and chronic migraine

Elisa Rubino,^1,2 Elisa Maria Piella,¹ Giulia Cicilese,^1,3 Silvia Boschi,¹ Alberto Mario Chiarandon,¹ Elena Tamagno,^1,3 Michela Guglielmotto,^1,3 Innocenzo Rainero^1,2 | ¹Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Turin, Italy; ²Headache Center, Department of Neuroscience and Mental Health, AOU Città della Salute e della Scienza di Torino; ³Neuroscience Institute Cavalieri Ottolenghi (NICO), Orbassano (TO), Italy

Background: microRNAs (miRNAs) play a crucial role in migraine pathophysiology through the regulation of inflammatory and neurovascular pathways. Among these, miR-30a has been implicated in modulating the expression of CALCA, the gene encoding CGRP. While reduced miR-30a levels have been reported in migraine patients compared to healthy controls, its role across clinical subtypes remains poorly defined. The main aim of our study was to investigate whether baseline plasma levels of miRNA-30a were different from clinical subgroups, and whether miR-30a may predict the clinical response to anti-CGRP mAbs in patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM). The second aim was to correlate miR-30a to CGRP concentrations in the same cohort of patients.

Methods: A prospective, longitudinal study was conducted on 37 patients with HFEM and CM (30 females, 7 males; 17 HFEM, 20 CM) treated with erenumab, eptinezumab, fremanezumab, or galcanezumab. Clinical outcomes, including monthly migraine days (MMD), Migraine Disability Assessment (MIDAS), and pain intensity (NRS), were assessed at baseline (T0), 3 months (T1), and 6 months (T2). Total RNA was extracted from plasma and reverse transcribed. The expression of miR-30a was quantified using quantitative PCR and normalized to the U6 housekeeping gene using the ΔCt method. Plasma CGRP were quantified by ELISA.

Results: CM patients showed significantly higher miRNA-30a expression than HFEM (ΔCt p=0.043). In HFEM patients, miRNA-30a levels correlated with CGRP concentrations (r=0.95, p=0.0012), while no correlation was observed in CM. Across the cohort, higher baseline miR-30a expression was associated with greater pain reduction at T2 (ΔNRS, r=+0.53, p=0.024) and with lower baseline MIDAS (r=–0.49, p=0.042).

Conclusion: Our study showed higher levels of miR-30a in patients with CM in respect to HFEM, indicating higher miRNA-30a expression in chronic forms. This difference, not previously reported, may reflect a compensatory regulatory mechanism in response to prolonged CGRP-related neuroinflammation. In our cohort, miRNA-30a correlated with CGRP levels in HFEM but not in CM, potentially indicating a disruption in regulatory coupling in the chronic stage of disease. Furthermore, baseline miR-30a levels may have predictive value for clinical response to anti-CGRP treatment. Further studies are needed to confirm our findings.