Biomarkers of MS therapies

Abstract

As more therapies become available for the treatment of MS, developing predictive biomarkers of treatment response is an unmet need. Potential immunological, pharmacogenomics and proteomic biomarkers of MS therapies will be reviewed. We have recently identified two HLA-class II haplotypes as potential biomarkers of clinical response to glatiramer acetate(GA): HLA DR 15+DQ6+; DR17-DQ2− was associated with a favorable response (71%) where as HLA DR15-DQ6-;DR17+DQ2+ was associated with a poor response. A simplified binary predictor (AUC 0.81-0.85) of response to GA involving an increase in IL-10 or IL-4, and reduction in IL18, caspase 1, or TNF-a at 3–6 months into treatment will be discussed. We have also reported significantly higher IL-17A levels at Month 6 ( p =0.036) in relapsing patients treated with IFNβ-1b for 12 months while BDNF levels were significantly higher at Month 3 ( p =0.028) in relapse-free subjects. Change from baseline in IL-4 levels inversely correlated with disability scores whereas change from baseline in IL-10/IFN-gamma ratio inversely correlated with occurrence of relapses. CXCR3+CD8+ T-cells tended to be higher but declined with treatment in relapse-free compared with relapsing subjects. Promising potential biomarkers of response to Natalizumab and its PML complication will be discussed.