Pathophysiology of inflammation and tissue injury in multiple sclerosis: what are the targets for therapy.

Many new therapies have become available for multiple sclerosis patients during the last decade. They are mainly effective in the early relapsing stage of the disease. Despite this undisputed progress, there are still major deficits in the treatment of the patients. Effective anti-inflammatory treatments profoundly decrease disease activity, although this may occur on the expense of a partially impaired immune surveillance of the central nervous system. Furthermore, the clinical outcome of recent trials does not always meet the expectations of the neuroimmunological community. This suggests that preclinical testing in experimental models, although useful and necessary, has its limitations. For treatment of the progressive stage of the disease blood brain barrier penetration of drugs appears to be one crucial issue. Additionally, little is known on the immunological mechanisms of slow burning inflammation present in the brain of patients with progressive MS. Finally, it is suggested that neuroprotective strategies, which target mitochondrial injury and its downstream effects on neurons and axons are promising future therapeutic options.