Development of biomarkers for multiple sclerosis as a neurodegenerative disorder

Multiple sclerosis (MS) is the most common neurological disorder leading to permanent disability in young adults in the developed world. While traditionally conceived as an autoimmune inflammatory disease it is becoming increasingly evident that axonal and neuronal degeneration occur, at least partly independent of inflammation, and already at the earliest stages of the disease. In addition, it is the progressive neurodegeneration which determines the amount of accumulating clinical disability. Therefore, MS should be considered as a neurodegenerative disorder. Development of disease-modifying drugs to treat MS is currently highly dynamic. Already, several drugs have shown short-term efficacy to delay progression of clinical disability, but the ultimate aim is to halt disease progression. In this context, the development of sensitive, reliable and valid biomarkers to measure neurodegeneration is an indispensible need to facilitate successful informative clinical trials. While no such biomarker is currently fully established, several promising candidate biomarkers obtained with multimodal techniques, including cerebrospinal fluid and serum analysis, neuroimaging and neurophysiology, are presently developed and evaluated. This paper compiles an up-to-date critical review of the available knowledge of candidate biomarkers of neurodegenerative processes in MS.

► Neurodegeneration is prevalent in all stages of multiple sclerosis (MS). ► Ongoing extensive research discovers biomarkers of neurodegeneration in MS. ► Validated biomarkers will be surrogate endpoints in future pivotal clinical trials. ► Validated biomarkers can assess neuroprotective efficacy of disease-modifying drugs.