Development of biomarkers in multiple sclerosis

Multiple sclerosis is a complex disease, as several patho-physiological processes (including in¯ammation, demye-lination, axonal damage and repair mechanisms) participate in the disease process. Furthermore, as new pathological evidence reveals, these processes are not uniformly represented across patient populations but can selectively predominate in individual patients, thus contributing to the heterogeneity in phenotypic expres-sion of the disease, its prognosis and response to therap-ies. While the armamentarium of available therapies for multiple sclerosis broadens, little is known about factors that predict treatment response in individual patients to a speci®c drug. More importantly, we are beginning to understand that, analogous to cancer ther-apy, the successful therapeutic strategy in multiple sclerosis might ultimately involve the combination of different therapeutics targeting several dominant patho-physiological processes. The development of these pro-cess-speci®c therapies will be impossible without the use of biomarkers that re¯ect the targeted process, can select patient population in which the targeted process is prevailing and can aid during the more rapid screen-ing of therapeutic agents in the early phase of their development. This review summarizes the general con-cepts of biomarkers and their potential use as surrogate endpoints and tailors these concepts to speci®c applica-tions in multiple sclerosis research