"Longitudinal Analysis of Amylin Levels in Migraine Patients Undergoing an Anti- CGRP/CGRPr Treatment"

Migraine, a complex and multifaceted disorder, remains only partially understood, with therapeutic strategies often limited by individual variability in response. While targeting calcitonin gene-related peptide (CGRP) has transformed migraine management, approximately half of patients with therapies targeting the CGRP pathway experience insufficient relief, suggesting other molecular players in migraine pathophysiology may be overlooked. Emerging evidence highlights amylin, a peptide of the calcitonin family, as a promising candidate with potential mechanistic overlap with CGRP. Canonical receptor of amylin is known to interact with CGRP, and both peptides are expressed in structures relevant to migraine. Preliminary clinical findings suggest that amylin might be involved in migraine pathophysiology by developing attacks and contributing to chronification of the condition; however, its exact impact and clinical relevance remain unverified. This prospective, monocentric, cross-sectional pilot study aims to deepen our understanding of the role of amylin in chronic migraine and anti-CGRP treatment outcomes. Specifically, we will (1) measure baseline interictal serum amylin levels in chronic migraine patients receiving anti-CGRP or CGRP receptor monoclonal antibody (mAb) therapy and a group of controls matched by sex and age, (2) monitor changes in amylin levels after six months of treatment, and (3) assess the correlation between amylin levels and clinical outcomes. We hypothesize that baseline amylin levels will be elevated in migraine patients and will normalize following effective treatment, aligning with improved clinical outcomes. Conversely, persistently elevated amylin levels may correlate with poorer response rates, potentially explaining the variability of treatment outcome found in the migraine population.