Diagnostic use of metabolomics in multiple sclerosis and its mimics

Tianrong Yeo1,2; Fay Probert1; Maciej Jurynczyk3; Megan Sealey1; Ruth Geraldes3; Ana Cavey3; Timothy D. W. Claridge4; Patrick Waters3; M. Isabel Leite3; Gabriele DeLuca3; Daniel C. Anthony1; Jacqueline Palace3 

1Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT UK
2Department of Neurology, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore
3Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Level 3, West Wing, Headley Way, Oxford, OX3 9DU UK
4Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA UK 

The complexity and heterogeneity of MS makes the development of a single candidate biomarker reflecting underlying disease processes difficult, but it is possible that a combination of biomarkers i.e. such as one generated from metabolomics, may capture holistically the complex interplay between endogenous and exogenous factors. We demonstrated that serum metabolomics was able to distinguish accurately relapsing-remitting MS (RRMS) from secondary progressive MS (SPMS), or from healthy controls. This observation could help to provide robust inclusion criteria for entry into clinical trials and to identify SPMS patients who are most likely to benefit from disease modifying therapies (DMT). We are now actively investigating the use of metabolomics to differentiate MS patients from clinically relevant controls, as well as in clinically isolated syndrome (CIS) when patients present with their first attack. The metabolomics approach also has the potential to extend to related conditions like aquaporin-4 (AQP4) antibody (Ab) neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein (MOG)-Ab disease. The overlapping clinical features of RRMS, AQP4-Ab NMOSD and MOG-Ab disease mean that detection of disease-specific antibodies remains the gold standard in diagnostics. However, antibody levels may become undetectable after treatment or during remission, especially in MOG-Ab disease, making the diagnosis less easy. Using plasma metabolomics we can identify distinct, antibody-independent metabolic signatures of RRMS, AQP4-Ab NMOSD and MOG-Ab disease, and we are extending this approach to interrogate the ‘double seronegative’ patients, those without either AQP4-Ab or MOG-Ab, who present with overlapping MS and NMOSD clinical features.
Jurynczyk M … Anthony, Palace. Metabolomics reveals distinct, antibody-independent, molecular signatures of MS, AQP4-antibody and MOG-antibody disease. Acta Neuropathol Commun. 2017 Dec 6;5(1):95.
Dickens……. Palace, Anthony, Sibson. A type 2 biomarker separates relapsing-remitting from secondary progressive multiple sclerosis.Neurology. 2014 Oct 21;83(17):1492-9