Multiple sclerosis (MS) is an important cause of progressive neurological disability, typically commencing in early adulthood. There is a need for safe and effective
therapy to prevent the progressive central nervous system (CNS) damage and resultant disability that characterize the disease course. Increasing evidence supports a chronic autoimmune basis for CNS damage in MS. In the present study, we review current concepts of autoimmune pathogenesis in MS, assess current
therapies aimed at countering autoimmune attack and discuss potential therapeutic strategies. Among currently available
therapies,
beta-interferon and
glatiramer acetate have a modest effect on reducing relapses and slowing the accumulation of disability in relapsing-remitting MS.
Beta-interferon is of doubtful efficacy in secondary progressive MS and appears to aggravate primary progressive MS, possibly by increasing antibody-mediated CNS damage through inhibition of B-cell apoptosis.
Mitoxantrone may reduce relapses and slow disability progression in relapsing-remitting and secondary progressive MS, but its use is limited by the risk of
cardiomyopathy. There are currently no effective treatments for primary progressive MS. Many
therapies that are effective in the animal model,
experimental autoimmune encephalomyelitis (EAE), are either ineffective in MS or--in the case of
gamma-interferon,
lenercept and altered
peptide ligands--actually make MS worse. This discrepancy may be explained by the occurrence in MS of defects in immunoregulatory mechanisms, the integrity of which is essential for the efficacy of these treatments in EAE. It is likely that the development of safe, effective
therapy for MS will depend on a better understanding of immunoregulatory defects in MS.