Quo vadis multiple sclerosis?

Excerpt

Multiple sclerosis (MS) is a disease that currently defies attempts to provide meaningful therapy. Four major issues still elude the neurological community (Steiner and Wirguin 2000): (1) Is it a disease or are we grouping together various disease entities, hence is it a syndrome? (2) What should be the diagnostic criteria of MS? The current ones enable recruiting into clinical trials an extremely heterogeneous population of patients associated with a too significant biological noise to enable true assessment of causative, prognostic and natural course parameters as well as the impact of the various therapeutic modalities. (3) What is the etio-pathogenesis of the condition? While the dogma has it that MS is an autoimmune state (Frohman et al. 2005), none of the criteria required for such a classification (identifying the auto-antigen, a reliable animal model, recognition of the type of immune response responsible for tissue damage, passive transfer and significant response to immunotherapy) has been met. A more recent set of eight criteria that added association with other immune-mediated conditions and correlation of the severity of the immune response with disease clinical activity has not been fulfilled either (Rodriguez 2009; Sriram and Steiner 2005). (4) What should be the surrogate markers and the primary and secondary end points in clinical trials that examine the impact of therapeutic modalities upon disease activity and course (Brown et al. 2007)? …