title: Monoclonal antibodies and recombinant immunoglobulins for the treatment of multiple sclerosis.
abstract: 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.
authors.affiliation: Neurology, Department of Medicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Henrik
authors.initials: H
authors.lastname: Gensicke
authors.forename: David
authors.initials: D
authors.lastname: Leppert
authors.forename: Özgür
authors.initials: Ö
authors.lastname: Yaldizli
authors.forename: Raija L P
authors.initials: RL
authors.lastname: Lindberg
authors.forename: Matthias
authors.initials: M
authors.lastname: Mehling
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.forename: Jens
authors.initials: J
authors.lastname: Kuhle
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D009103:Multiple Sclerosis / Q000276:immunology* / Q000628:therapy*; D000069442:Natalizumab; D011994:Recombinant Proteins / Q000008:administration & dosage; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000069442:Natalizumab; D011994:Recombinant Proteins; D000069283:Rituximab; C575974:tabalumab