Monoclonal Antibodies in Multiple Sclerosis: Present and Future

Abstract

The global incidence of multiple sclerosis (MS) appears to be increasing. Although it may not be associated with a high mortality rate, this disease has a high morbidity rate which affects the quality of life of patients and reduces their ability to do their activities of daily living. Thankfully, the development of novel disease modifying therapies continues to increase. Monoclonal antibodies (MABs) have become a mainstay of MS treatment and they are likely to continue to be developed for the treatment of this disease. Specifically, MABs have proven to be some of the most efficacious treatments at reducing relapses and the inflammation in MS patients, including the first treatment for primary progressive MS and are being explored as reparative/remyelinating agents as well. These relatively new treatments will be reviewed here to help evaluate their efficacy, adverse events, immunogenicity, and benefit-risk ratios in the treatment of the diverse spectrum of MS. The focus will be on MABs that are currently approved or may be approved in the near future.

Keywords: Ocrevus; Rituxan; Tysabri; anti-CD20; clinical trial; disease modifying therapy; monoclonal antibodies; multiple sclerosis.

Figure 1

Bioengineering techniques have resulted in progressively more humanized antibodies. The figure shows the different fractions of the monoclonal antibodies and whether they represent mouse (green) or human (blue) sequences. As the sequences become more humanized their immunogenicity decreases. Glycosylation occurs at amino acid N297 and affects ADCC. Fragment antigen binding (Fab), Fragment crystallizable (Fc), Antigen-dependent cellular cytotoxicity (ADCC).

Figure 2

Mechanism of action of monoclonal antibodies in the treatment of multiple sclerosis. Ocrelizumab, rituximab, ofatumumab and ublituximab target CD20 expressing cells. Natalizumab targets transmigration of lymphocytes through the blood brain barrier. Alemtuzumab targets CD52 expressing cells. Opicinumab helps OPC differentiate into myelin producing OLGs. Cluster of differentiation (CD), T helper cells (Th), Leucine rich repeat and Immunoglobin-like domain-containing protein 1 (LINGO-1), oligodendrocyte (OLG), oligodendrocyte precursor cell (OPC).