A framework for blood biomarker discovery in MS

Multiple sclerosis (MS) biomarkers hold potential for improving pathophysiological understanding, diagnostics, prognostication, and treatment personalisation. Technological advances now permit detection of blood biomarkers at previously prohibitively low concentrations. Concentrations of several candidate biomarkers have been shown to correlate between blood and cerebrospinal fluid (CSF). The development of '-omics' panel-based technologies now facilitates the discovery of collections of molecules, the interdependency of which may better reflect disease heterogeneity. Neurofilament light (NfL) is the clearest example of the success of a biomarker entering the realm of clinical practice in MS, with promising developments in others such as glial fibrillary acid protein (GFAP). However, integration of new biomarkers requires standardisation of discovery and validation across the various available technologies, along with demonstration of clinical utility, to gain regulatory approval and widespread adoption. In this review, focused on blood-based biomarkers, we expand on the above discoveries, developments and trajectories, to provide a framework for understanding this crucial body of work.