As therapeutic options for multiple sclerosis widen, validated biomarkers of clinical disease activity are urgently needed. Reliable biomarkers would assist in choosing initial therapy, monitoring response to therapy, detecting subclinical disease activity, predicting and possibly preventing therapeutic failure, and hopefully improving both short (relapses) and long-term (disability) outcomes. The presence of oligoclonal bands in the cerebrospinal fluid is a well-validated biomarker that is useful in initial diagnosis. Neutralizing antibodies to interferon-beta are also useful in identifying treatment failure and possibly guiding changes in therapy. The discovery of antibodies to aquaporin-4 in patients with neuromyelitis optica delineates patients with a fundamentally different underlying pathophysiology and clinical course who may require alternate therapeutic approaches. While numerous other candidate biomarkers in serum and cerebrospinal fluid have been described, none so far have the validated reliability necessary for widespread clinical use. The availability of multiple genetic and protein microarray technology may assist in identifying more reliable candidate biomarkers or patterns of multiple biomarkers and improve specificity. The heterogeneity of multiple sclerosis may necessitate individualized biomarkers and therapeutic decisions within distinct subsets of patients.
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