Background: Multiple sclerosis (MS) lacks reliable biomarkers that reflect disease activity. Recent evidence suggests that an altered sphingolipid metabolism is associated with MS pathogenesis. Objective: To explore acid sphingomyelinase (ASM) activity and altered sphingolipid metabolism as potential biomarkers in serum of MS patients, to predict active and progressive disease, and response to disease modifying therapy (DMT). Methods: Levels of serum ASM activity were longitudinally analyzed in 40 clinically isolated syndrome, 64 relapsing remitting (RR) and 10 primary progressive MS patients, and 22 healthy controls (HC). ASM activity and sphingolipid levels were measured in a different sample of 61 RRMS patients using DMT. Results: A significant difference in ASM activity levels was observed between MS patients and HC (p < 0.001). There was no correlation between ASM activity levels and disease activity, progression or response to DMT. Ceramide (Cer)-C16:0, Cer-C24:0 and sphingomyelin (SM)-C20:0, SM-C22:0, SM-C24:0 and SM-C24:1 showed a significant increase during fingolimod use. Conclusion: Although higher levels in MS patients were found, ASM activity levels do not show potential as a biomarker for predicting disease activity, progression or response to DMT. Two ceramides and four types of sphingomyelin require further investigation as potential markers for treatment response.

, , , ,,
Multiple Sclerosis and Related Disorders
Department of Internal Medicine

Leurs, C.E. (C. E.), Lopes Pinheiro, M. A., Wierts, L. (L.), den Hoedt, S. (S.), Mulder, M.T. (M. T.), Eijlers, A.J.C. (A. J.C.), … de Vries, H.E. (H. E.). (2019). Acid sphingomyelinase: No potential as a biomarker for multiple sclerosis. Multiple Sclerosis and Related Disorders, 28, 44–49. doi:10.1016/j.msard.2018.11.024