Pregnancy and multiple sclerosis: from molecular mechanisms to clinical application

Translational research generally refers to a "bench to bedside" approach where basic science discoveries in models move to clinical trials in humans. However, a "bedside to bench to bedside" approach may be more promising with respect to clinical relevance, since it starts with a clinical observation that can serve as a research paradigm to elucidate mechanisms and translate them back into novel therapeutic approaches. The effect of pregnancy on human autoimmune disorders in general, and multiple sclerosis (MS) in particular, serves as an intriguing example of how this can be used to understand disease pathobiology and discover new therapeutic targets. Disease activity in MS undergoes pronounced shifts in the time before, during, and after pregnancy. The most well-known and established example is a reduction in relapse rates in the last trimester by 70-80 %. However, disease activity reappears in the first few months after delivery, temporarily overshooting pre-pregnancy levels. This phenomenon has since its first description served as a model for investigating novel treatment options in animal models and has cumulated in successful phase 2a and 2b trials in female MS patients. However, recently, a number of other clinical observations have been made that might be similarly suitable to offer additional insights into pathobiological mechanisms of MS activity, progression, and possibly even incidence. Here, we outline the various changes in the clinical course of MS that have been described in relation to pregnancy, both short term and long term, and discuss how these may inform the development of novel treatments for autoimmune diseases.