Monoclonal antibodies in multiple sclerosis treatment: current and future steps.

Abstract

Multiple sclerosis (MS) is an autoimmune disease in which autoreactive T cells cross the blood—brain barrier and attack the myelin sheath leading to a cascade of inflammation. The result is demyelination, acute axonal transection, gliosis and subsequent axonal degeneration [Trapp et al. 1998]. Unpredictable episodes of neurological disability in young adults are followed by a gradual accumulation of deficits over time as the disease switches from an inflammatory to a degenerative ‘secondary progressive’ phase. Monoclonal antibodies have been used as experimental treatments of MS since the 1980s. Their advantage is high specificity for their target; their disadvantages are that they (usually) require intravenous administration, often are associated with infusion reactions and, as large foreign proteins, they are immunogenic. Past experience with monoclonal antibodies has taught researchers to interpret results seen in animal models with caution. Anti-TNFα antibodies are successful in the treatment of rheumatoid arthritis and work done using the animal model of MS (experimental autoimmune encephalomyelitis, EAE) suggested a beneficial effect on the disease. Early trials in MS patients, however, showed the opposite effect with worsening of disease activity [Lenercept Multiple Sclerosis Study Group and the University of British Columbia MS/MRI Analysis Group, 1999]. There have also been reports of de novo MS occurring in rheumatoid arthritis patients treated with anti-TNFα therapy [Sicotte and Voskuhl, 2001]. Data from clinical research trials has however given important insights in to the underlying disease mechanism and suggests that treating MS in the early inflammatory phase gives an opportunity to delay or prevent the onset of disease progression [Coles et al. 2006]. To date only one monoclonal antibody has been licensed as a treatment for MS: natalizumab. Here we review the current and future use of monoclonal antibodies in MS (Table 1). Table 1. Current and future monoclonal antibodies in MS.