Alpha Calcitonin Gene-related Peptide, Neuropeptide Y, and Substance P as Biomarkers for Diagnosis and Disease Activity and Severity in Multiple Sclerosis

Background: Alpha calcitonin gene-related peptide (aCGRP), neuropeptide Y (NPY), and substance P (SP) are neuropeptides that have emerged recently as potent immunomodulatory factors with potential as novel biomarkers and therapeutic targets in multiple sclerosis (MS). Objective: The study aimed to detect serum levels of aCGRP, NPY, and SP in MS patients versus healthy controls and their association with disease activity and severity. Methods: Serum levels were measured in MS patients and age and sex-matched healthy controls using ELISA. Results: We included 67 MS patients: 61 relapsing-remitting MS (RR-MS) and 6 progressive MS (PR-MS), and 67 healthy controls. Serum NPY level was found to be lower in MS patients than in healthy controls (p < 0.001). Serum aCGRP level was higher in PR-MS compared to RR-MS (p = 0.007) and healthy controls (p = 0.001), and it positively correlated with EDSS (r = 0.270, p = 0.028). Serum NPY level was significantly higher in RR-MS and PR-MS than in healthy controls (p < 0.001 and p = 0.001, respectively), and it was lower in patients with mild or moderate/severe disease than in healthy controls (p < 0.001). Significant inverse correlations were found between SP level and MS disease duration (r = -0.279, p = 0.022) and duration of current DMT (r = -0.315, p = 0.042). Conclusion: Lower serum levels of NPY were revealed in MS patients compared to healthy controls. Since serum levels of aCGRP are significantly associated with disease activity and severity, it is a potential disease progression marker.