INTRODUCTION: Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating disease of the CNS and results in neurological disability. Existing immunomodulatory and immunosuppressive approaches lower the number of relapses but do not cure or reverse existing deficits nor improve long-term disability in MS patients. AREAS COVERED: Monogenic antibodies were described as treatment options for MS, however the immunogenicity of mouse antibodies hampered the efficacy of potential therapeutics in humans. Availability of improved antibody production technologies resulted in a paradigm shift in MS treatment strategies. In this review, an overview of immunotherapies for MS that use conventional monoclonal antibodies reactive to immune system and their properties and mechanisms of action will be discussed, including recent advances in MS therapeutics and highlight natural autoantibodies (NAbs) that directly target CNS cells. EXPERT OPINION: Recent challenges for MS therapy are the identification of relevant molecular and cellular targets, time frame of treatment, and antibody toxicity profiles to identify safe treatment options for MS patients. The application of monoclonal antibody therapies with better biological efficacy associated with minimum side effects possesses huge clinical potential. Advances in monoclonal antibody technologies that directly target cells of nervous system may promote the CNS regeneration field from bench to bedside.

Center for Regenerative Medicine Neuroregeneration Mayo Clinic 200 1st Street SW Rochester MN 55905 USA

Department of Biomedical Engineering University of Minnesota 200 Union Street SE 4 174 Keller Hall Minneapolis MN 55455 USA

Department of Electrical and Computer Engineering University of Minnesota 200 Union Street SE 4 174 Keller Hall Minneapolis MN 55455 USA

Department of General Medicine Charles University Prague Faculty of Medicine in Hradec Kralove Simkova 870 Hradec Kralove 1 500 38 Czech Republic

Department of Immunology Mayo Clinic 200 1st Street SW Rochester MN 55905 USA

Department of Neurologic Surgery Mayo Clinic 200 1st Street SW Rochester MN 55905 USA

Department of Neurology Mayo Clinic 200 1st Street SW Rochester MN 55905 USA

Department of Neuroscience Mayo Clinic 4500 San Pablo Road S Jacksonville FL 32224 USA

Department of Physiology and Biomedical Engineering Mayo Clinic 200 1st Street SW Rochester MN 55905 USA

Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology Mayo Clinic 200 1st Street SW Rochester MN 55905 USA

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