Monoclonal Antibodies and Recombinant Immunoglobulins for the Treatment of Multiple Sclerosis

• Published in: CNS drugs 2012, Vol.26 (1), p.11-37
• Main Authors: Gensicke, Henrik, Leppert, David, Yaldizli, Özgür, Lindberg, Raija L. P., Mehling, Matthias, Kappos, Ludwig, Kuhle, Jens
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Murine-Derived - administration & dosage; Biological and medical sciences; Cell adhesion & migration; Disease; Drug Delivery Systems - methods; Drug dosages; Humans; Immunomodulators; Lymphocytes; Medical sciences; Medicine; Medicine & Public Health; Monoclonal antibodies; Multiple sclerosis; Multiple Sclerosis - immunology; Multiple Sclerosis - therapy; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Natalizumab; Neurology; Neurosciences; Pharmacology. Drug treatments; Pharmacotherapy; Psychiatry; Psychopharmacology; Recombinant Proteins - administration & dosage; Review Article; Rituximab; Treatment Outcome
• ISSN: 1172-7047; 1179-1934
• DOI: 10.2165/11596920-000000000-00000

Multiple sclerosis (MS) is an inflammatory and degenerative disease leading to demyelination and axonal damage in the CNS. Autoimmunity plays a central role in MS pathogenesis. Per definition, monoclonal antibodies are recombinant biological compounds with a well defined target, thus carrying the promise of targeting pathogenic cells or molecules with high specificity, avoiding undesired off-target effects. Natalizumab was the first monoclonal antibody to be approved for the treatment of MS. Several other monoclonal antibodies are in development and have demonstrated promising efficacy in phase II studies. They can be categorized according to their mode of action into compounds targeting (i) leukocyte migration into the CNS (natalizumab); (ii) cytolytic antibodies (rituximab, ocrelizumab, ofatumumab, alemtuzumab); or (iii) antibodies and recombinant proteins targeting cytokines and chemokines and their receptors (daclizumab, ustekinumab, atacicept, tabalumab [Ly-2127399], secukinumab [AIN457]). In this review, we discuss the specific molecular targets, clinical efficacy and safety of these compounds and discuss criteria to anticipate the position of monoclonal antibodies in the diversifying armamentarium of MS therapy in the coming years.