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Annu Rev Med. 2007;58:417-32.

New therapeutic approaches for multiple sclerosis.

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Center for Neurologic Diseases, Department of Neurology, Brigham & Women's Hospital, Boston, Massachusetts 02115, USA.


Although several therapies exist for multiple sclerosis (MS), the most common inflammatory demyelinating disease of the central nervous system (CNS), there remains a large unmet clinical need for more effective immunomodulatory treatments in this category of diseases and for interventions that address their neurodegenerative component, which is currently untreated. Progress in our understanding of the immunology of MS over the past 30 years has recently synergized with novel computational methods and emerging high-throughput technologies that characterize variations in DNA, RNA, proteins, and metabolites to usher in a period of intense pathophysiologic investigation. These efforts are beginning to define subsets of patients with different forms of demyelinating disease. This partitioning of patients will prove valuable as we begin to tailor immunotherapy to the underlying pathophysiologic processes of individual patients using current therapies, emerging treatments, and rational combinations of all of these treatments. Preventing the entry of lymphocytes into the CNS and modifying the nature of the immune response are treatment approaches that work in the inflammatory component of MS but have little or no effect on neurodegeneration. Two challenges confront us: to develop cocktails of therapies that shift the immune homeostasis of patients with MS toward a healthy profile, and to identify and modulate the activity of targets within the neurodegenerative component of MS.

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