Knowns and unknowns in the future of multiple sclerosis treatment.

Multiple sclerosis is a chronic disease confined to the central nervous system. Its pathological hallmarks are neuroinflammation, de- and re-myelination, neurodegeneration and astrogliosis. The aetiology of multiple sclerosis is unknown, although a growing body of evidence supports an autoimmune pathogenesis triggered by environmental factors in genetically susceptible individuals. It is therefore perhaps unsurprising that immunomodulatory therapies have now been the mainstay of pharmacotherapy and the focus for the search for a cure for many decades. Currently, clinicians have access to two distinct treatment strategies, namely general immunomodulation or immunosuppression. During the last two decades, several immunomodulatory agents and one immunosuppressant drug have been shown to be effective in clinical trials and have been approved on this basis for the treatment of multiple sclerosis. Current drugs offer well-established safe and effective therapeutic agents for multiple sclerosis in both the short and long term. More recently, growing knowledge of specific anatomical, cellular and molecular targets that play critical roles in the inflammatory cascade of multiple sclerosis have shifted the focus of drug development towards specific targets. Future multiple sclerosis therapies arising from this research may offer better suppression of disease activity, but may be associated with potentially severe side-effects in some patients that may be difficult to manage. In the near future, better understanding of the pathogenesis of multiple sclerosis will probably allow the development of even more effective agents for all clinical phenotypes of the disease. Future therapeutic agents will also have to be designed to address the neurodegenerative component of the physiopathology of multiple sclerosis.