Molecular biomarkers in multiple sclerosis

Abstract

Multiple sclerosis (MS) is an inflammatory-neurodegenerative disease of the central nervous system presenting with significant inter- and intraindividual heterogeneity. However, the application of clinical and imaging biomarkers is currently not able to allow individual characterization and prediction. Complementary, molecular biomarkers which are easily quantifiable come from the areas of immunology and neurobiology due to the causal pathomechanisms and can excellently complement other disease characteristics. Only a few molecular biomarkers have so far been routinely used in clinical practice as their validation and transfer take a long time. This review describes the characteristics that an ideal MS biomarker should have and the challenges of establishing new biomarkers. In addition, clinically relevant and promising biomarkers from the blood and cerebrospinal fluid are presented which are useful for MS diagnosis and prognosis as well as for the assessment of therapy response and side effects.

Keywords: Cerebrospinal fluid; Molecular biomarker; Multiple sclerosis; Neurofilament; Oligoclonal bands; Treatment response.

Fig. 1

Different types of biomarkers in multiple sclerosis: Diagnostic biomarkers are used to confirm the diagnosis of MS. A test used to diagnose a disease often measures a type of biomarker called a “surrogate.” Diagnostic biomarkers may facilitate earlier detection of a disorder than can be achieved by other approaches. A prognostic biomarker helps to indicate how a disease may develop in an individual when a disorder is already diagnosed. The presence or absence of a prognostic marker can be useful for the selection of patients for treatment but does not directly predict the response to a treatment. This is more specified by the predictive biomarker which helps to determine which patients are most likely to benefit from a specific treatment option. Predictive diagnostics can provide information about how well a treatment is likely to work in a particular patient or about the likelihood of that treatment causing an unwanted side effect. For prognosis and prediction, disease activity biomarkers comprise biomarkers to measure inflammatory and/or neurodegenerative components of disease. For personalized MS treatment, treatment-response biomarkers could be helpful to differentiate patients regarding their outcome related to efficacy and side effects (treatment responders and non-responders as well as patients with and without adverse drug reactions). In addition, these treatment-response markers could be applicable for all treatments or be specific for a specific treatment only