, Volume 16, Issue 3, pp 797–807 | Cite as

Assessing the Metabolomic Profile of Multiple Sclerosis Patients Treated with Interferon Beta 1a by 1H-NMR Spectroscopy

  • Lorena LoreficeEmail author
  • Federica Murgia
  • Giuseppe Fenu
  • Jessica Frau
  • Giancarlo Coghe
  • Maria Rita Murru
  • Stefania Tranquilli
  • Andrea Visconti
  • Maria Giovanna Marrosu
  • Luigi Atzori
  • Eleonora Cocco
Original Article


Metabolomic research has emerged as a promising approach to identify potential biomarkers in multiple sclerosis (MS). The aim of the present study was to determine the effect of interferon beta (IFN ß) on the metabolome of MS patients to explore possible biomarkers of disease activity and therapeutic response. Twenty-one MS patients starting IFN ß therapy (Rebif® 44 μg; s.c. 3 times per week) were enrolled. Blood samples were obtained at baseline and after 6, 12, and 24 months of IFN ß treatment and were analyzed by high-resolution nuclear magnetic resonance spectroscopy. Changes in metabolites were analyzed. After IFN ß exposure, patients  were divided into responders and nonresponders according to the “no evidence of disease activity” (NEDA-3) definition (absence of relapses, disability progression, and magnetic resonance imaging activity), and samples obtained at baseline were analyzed to evaluate the presence of metabolic differences predictive of IFN ß response. The results of the investigation demonstrated differential distribution of baseline samples compared to those obtained during IFN ß exposure, particularly after 24 months of treatment (R2X = 0.812, R2Y = 0.797, Q2 = 0.613, p = 0.003). In addition, differences in the baseline metabolome between responder and nonresponder patients with respect to lactate, acetone, 3-OH-butyrate, tryptophan, citrate, lysine, and glucose levels were found (R2X = 0.442, R2Y = 0.768, Q2 = 0.532, p = 0.01). In conclusion, a metabolomic approach appears to be a promising, noninvasive tool that could potentially contribute to predicting the efficacy of MS therapies.

Key Words

Multiple sclerosis metabolomic analysis biomarkers interferon beta 1a treatment monitoring 



The authors thank Merck Serono for the financial support.

Required Author Forms

Disclosure forms provided by the authors are available with the online version of this article.

Compliance with Ethical Standards

The local institutional Ethics Committee approved the study, and written informed consent was obtained from each participant prior to participation.

Conflict of Interest

L. Lorefice received a speaker fee from Teva and serves on scientific advisory boards for Merck Serono and Biogen.

G. Fenu received honoraria for consultancy from Novartis and for speaking from Merck Serono, Biogen, and Teva.

J. Frau serves on scientific advisory boards for Biogen and Genzyme and received honoraria for speaking from Merck Serono and Teva.

G. Coghe received speaker fees from Teva and Almirall.

A. Visconti is a full time employee to Merck Serono.

L. Atzori, F. Murgia, M. Murru, and S. Tranquilli have nothing to disclose.

M. Marrosu and E. Cocco have received honoraria for consultancy or speaking from Bayer, Biogen, Novartis, Sanofi, Genzyme, Serono, and Teva.

Supplementary material

13311_2019_721_MOESM1_ESM.pdf (14.2 mb)
ESM 1 (PDF 14524 kb)


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Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2019

Authors and Affiliations

  • Lorena Lorefice
    • 1
    Email author
  • Federica Murgia
    • 1
  • Giuseppe Fenu
    • 1
  • Jessica Frau
    • 1
  • Giancarlo Coghe
    • 1
  • Maria Rita Murru
    • 1
  • Stefania Tranquilli
    • 1
  • Andrea Visconti
    • 2
  • Maria Giovanna Marrosu
    • 1
  • Luigi Atzori
    • 3
  • Eleonora Cocco
    • 1
  1. 1.Multiple Sclerosis Centre, Department of Medical Sciences and Public Health, Binaghi HospitalUniversity of CagliariCagliariItaly
  2. 2.Merck Serono S.p.A.RomeItaly
  3. 3.Department of Biomedical SciencesUniversity of CagliariCagliariItaly

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